Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.78728122
Both DR 4 and KILLER / DR5 independently bind to their specific ligand TRAIL and engage the caspase cascade to induce apoptosis . 0.78728122^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
These include Fas , TNF R 1 , lymphocyte associated receptor of death ( LARD ) , DR 4 , and TNF related apoptosis inducing ligand receptor inducer of cell killing 2 ( TRICK 2 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here we report that Apo 2L is expressed and utilized by human Natural Killer ( NK ) cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Protocols are given for a specific ligand receptor pair , namely TRAIL ( Apo 2L ) and TRAIL receptor 2 ( DR 5 ) , but can be applied to other ligands and receptors of the TNF family . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Antileukemic drugs increase death receptor 5 levels and enhance Apo 2L induced apoptosis of human acute leukemia cells . ^^^ Susceptibility of these acute leukemia cell types , which are known to lack p 53 ( wt ) function , did not appear to correlate with the levels of the apoptosis signaling death receptors ( DRs ) of Apo 2L , ie , DR 4 and DR 5 ; decoy receptors ( DcR 1 and 2 ) ; FLAME 1 ( cFLIP ) ; or proteins in the inhibitors of apoptosis proteins ( IAP ) family . ^^^ Treatment of human leukemic cells with etoposide , Ara C , or doxorubicin increased DR 5 but not DR 4 , Fas , DcR 1 , DcR 2 , Fas ligand , or Apo 2L levels . ^^^ These findings indicate that treatment with etoposide , Ara C , or doxorubicin up regulates DR 5 levels in a p 53 independent manner and sensitizes human acute leukemia cells to Apo 2L induced apoptosis . ( Blood . 2000 ; 96 : 3900 3906 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Apo 2 ligand / TNF related apoptosis inducing ligand and death receptor 5 mediate the apoptotic signaling induced by ionizing radiation in leukemic cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Apo 2 ligand tumor necrosis factor related apoptosis inducing ligand ( Apo2L / TRAIL ) is a member of the tumor necrosis factor family that interacts with cell surface `` death receptors ' ' ( DR 4 and DR 5 ) to initiate programmed cell death . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
DR 5 ( also called TRAIL receptor 2 and KILLER ) is an apoptosis inducing membrane receptor for tumor necrosis factor related apoptosis inducing ligand ( also called TRAIL and Apo 2 ligand ) . ^^^ DR 5 ( also called TRAIL receptor 2 and KILLER ) is an apoptosis inducing membrane receptor for tumor necrosis factor related apoptosis inducing ligand ( also called TRAIL and Apo 2 ligand ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We have cloned a new member of this family , TRICK 2 , the TRAIL ( TNF related apoptosis inducing ligand ) receptor inducer of cell killing 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Death receptors include tumor necrosis factor receptor 1 , Fas , death receptor ( DR ) 3 , DR 4 , DR 5 and DR 6 , whereas death ligands include tumor necrosis factor a , lymphotoxin , Fas Ligand , Apo 3 Ligand and TRAIL ( TNF Related Apoptosis Inducing Ligand ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Two additional members of this family , DR 4 and DR 5 , transduce apoptotic signals upon binding soluble TNF related apoptosis inducing ligand ( TRAIL ) that , like FasL , belongs to the growing TNF family of molecules . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Past studies have shown that apoptosis mediated by TNF related apoptosis inducing ligand ( TRAIL ) is regulated by the expression of two death receptors [ TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL R 2 ] and two decoy receptors ( TRAIL R 3 and TRAIL R 4 ) that inhibit apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we report that ( auto ) antigen specific human T cells are not killed in vitro by soluble TNF related apoptosis inducing ligand ( TRAIL ) although expressing death inducing receptors , TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TNF related apoptosis inducing ligand ( TRAIL ) is a more recently identified member of the TNF superfamily that has been shown to selectively kill neoplastic cells by engaging two cell surface receptors , DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL ( TNF related apoptosis inducing ligand ) induces apoptosis in susceptible cells by binding to death receptors 4 ( DR 4 ) and 5 ( DR 5 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TNF related apoptosis inducing ligand ( TRAIL / APO 2L ) is a typical member of the TNF ligand family that induces apoptosis by activating the death receptors TRAIL R 1 and TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Reverse transcriptase polymerase chain reaction ( RT PCR ) was applied to assay mRNA expression of TRAIl ( the TNF related apoptosis inducing ligand ) receptors ( DR 5 , DcR 1 , and DcR 2 ) in 3 cases of normal ovarian tissues , 6 cases of ovarian benign tumors , and 16 cases of ovarian cancers . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
CD 95 , TNF related apoptosis inducing ligand ( TRAIL R 1 ) , and TRAIL R 2 bind FADD directly , whereas recruitment to TNF R 1 is indirect through another adaptor TNF receptor associated death domain protein ( TRADD ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In this study , we examined the ability to eliminate the hyperplastic synovium by adenoviral mediated gene transfer of human TNF related apoptosis inducing ligand ( TRAIL ) , a member of the TNF family that is able to induce apoptosis through interaction with receptors containing death domains , DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL ( TNF related apoptosis inducing ligand ) induces apoptosis by cross linking of the two TRAIL receptors that contain a death domain , TRAIL R 1 and TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Death receptors [ Fas / Apo 1 / CD95 , TNF R 1 [ tumour necrosis factor ( TNF ) receptor 1 ] , DR 3 [ death receptor 3 ] , TRAIL R 1 [ TNF related apoptosis inducing ligand receptor 1 ] , TRAIL R 2 , DR 6 , p 75 NGFR [ p 75 nerve growth factor receptor ] , EDAR [ ectodermal dysplasia receptor ] ] form a subgroup of the TNF R superfamily that can induce apoptosis ( programmed cell death ) via a conserved cytoplasmic signalling module termed the death domain . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TNF related apoptosis inducing ligand ( TRAIL ) , also known as Apo2L , activates DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we show that malignant mesothelial ( MM ) cell lines as well as primary MM cells and normal mesothelial ( NM ) cells express Fas and TNF related apoptosis inducing ligand ( TRAIL ) receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL ( TNF related apoptosis inducing ligand ) death receptors DR 4 and DR 5 facilitate the selective elimination of malignant cells through the induction of apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Pretreating the cells with neutralizing antibodies to Fas , tumor necrosis factor ( TNF ) alpha receptor 1 , or TNF related apoptosis inducing ligand receptors ( DR 4 and DR 5 ) did not affect taxol induced apoptosis , but transfection of the cells with a dominant negative FADD plasmid resulted in inhibition of taxol induced apoptosis , revealing that taxol induces apoptosis independently of these death receptors but dependently on FADD . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Members of the tumor necrosis factor ( TNF ) superfamily of receptors such as Fas / CD95 and the TNF related apoptosis inducing ligand ( TRAIL ) receptors DR 4 and DR 5 induce apoptosis by recruiting adaptor molecules and caspases . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Fas ( CD 95 ) , FasL ( CD95L ) , and TRAIL ( TNF related apoptosis inducing ligand ) with its receptors DR 4 ( Death Receptor 4 ) , and DR 5 ( Death Receptor 5 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we show that caspase 8 activity is significantly increased , whereas the expression of death receptors other than Fas , including the type 1 receptor for tumor necrosis factor alpha ( TNF alpha ) and the receptors for the TNF related apoptosis inducing ligand ( TRAIL ) , DR 4 and DR 5 , was normal . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Immunohistochemistry displayed a greater amount of TNF related apoptosis inducing ligand ( TRAIL ) and KILLER , a key murine ligand and receptor involved in the extrinsic pathway , expressed in cumulus cells from hyperglycemic mice compared with controls , suggesting that this apoptotic pathway may be up regulated under diabetic stress . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Attenuating the GSK3beta FBW 7 axis results in stabilization of MYC , up regulation of surface levels of the TNF related apoptosis inducing ligand death receptor 5 , and potentiation of death receptor 5 induced apoptosis in vitro and in vivo . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Cytokines such as tumor necrosis factor alpha ( TNF alpha ) , FasL , and TNF related apoptosis inducing ligand ( TRAIL ) induce apoptosis or inflammation through binding to their specific receptors , TNFR 1 , Fas , and DR 5 , respectively . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
VSMCs sensitive to T cell mediated killing express the death receptor DR 5 ( TNF related apoptosis inducing ligand [ TRAIL ] receptor 2 ) , and anti TRAIL and anti DR 5 antibodies block T cell mediated apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
METHODS : We observed the cytotoxic effect of cytotoxic T lymphocyte ( CTL ) ( CD8+ ) and natural killer cells ( CD 3 CD16+ CD56+ ) toward chronic ITP patient ' s autologous platelets , and investigated the expression of Fas ligand ( FasL ) , tumor necrosis factor ( TNF ) alpha and TNF related apoptosis inducing ligand , as well as perforin and granzyme B mRNA in CD8+ cells using flow cytometry and reverse transcriptase polymerase chain reaction . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
BACKGROUND : As advanced prostate cancers are resistant to currently available chemotherapies , we evaluated the cytotoxic effect of TNF related apoptosis inducing ligand ( TRAIL ) and characterized the involvement of its five receptors DR 4 , DR 5 , DcR 1 , DcR 2 , and osteoprotegerin ( OPG ) and of the death inducing signaling complex ( DISC ) forming proteins caspase 8 and c FLIP in prostate cell lines . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here we show that induction of tumor cell apoptosis by an agonistic monoclonal antibody to DR 5 , the apoptosis inducing receptor for TNF related apoptosis inducing ligand ( TRAIL ) , combined with T cell activation by agonistic monoclonal antibodies to the costimulatory molecules CD 40 and CD 137 , potently and rapidly stimulated tumor specific effector CD8+ T cells capable of eradicating preestablished tumors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We isolated a number of small molecules that activate p 53 reporter activity , increase expression of p 53 target genes such as p 21 ( WAF 1 ) or death receptor 5 ( KILLER / DR5 ) of TNF related apoptosis inducing ligand ( TRAIL ) , and induce apoptosis in p 53 deficient cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
COX 2 inhibition triggered expression of the CD 95 , tumor necrosis factor ( TNF ) R , and TNF related apoptosis inducing ligand ( TRAIL ) R 1 and TRAIL R 2 death receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Three closely related receptors bind Apo2L : DR 4 and DR 5 , which contain cytoplasmic death domains and signal apoptosis , and DcR 1 , a decoy receptor that lacks a cytoplasmic tail and inhibits Apo2L function [ 3 5 ] . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
APO2L ( TRAIL ) is a novel CD95L ( Fas / APO 1 L ) homologous cytotoxic cytokine that interacts with various receptors which transmit ( DR 4 , DR 5 ) or inhibit ( DcR 1 , DcR 2 ) an apoptotic signal . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
AP 02 ligand ( APO2L ) is a CD 95 ligand ( CD95L ) related cytokine of the tumor necrosis factor family that interacts with agonistic ( DR 4 , DR 5 ) and antagonistic ( DcR 1 , DcR 2 ) receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Transfection experiments indicate that DcR 1 and DcR 2 act as decoys that prevent Apo2L from inducing apoptosis through DR 4 and DR 5 . ^^^ Similar to CD95L , Apo2L activates rapid apoptosis in many types of cancer cells ; however , whereas CD95L mRNA expression is restricted mainly to activated T cells , natural killer cells , and immune privileged sites , Apo2L mRNA occurs in a wide variety of tissues . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Expression of TRAIL ( Apo2L ) , DR 4 ( TRAIL receptor 1 ) , DR 5 ( TRAIL receptor 2 ) and TRID ( TRAIL receptor 3 ) genes in multidrug resistant human acute myeloid leukemia cell lines that overexpress MDR 1 ( HL60 / Tax ) or MRP ( HL60 / AR ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Although it is known that TRAIL ( Apo2L ) induces apoptosis and activates NF kappaB and Jun N terminal kinase ( JNK ) through receptors such as TRAIL R 1 ( DR 4 ) and TRAIL R 2 ( DR 5 ) , the components of its signaling cascade have not been well defined . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL ( tumour necrosis factor related apoptosis ligand or Apo2L ) triggers apoptosis through engagement of the death receptors TRAIL R 1 ( also known as DR 4 ) and TRAIL R 2 ( DR 5 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Cell death induced by IFNs and Apo2L in U 266 cells was partially blocked by a dominant negative Apo2L receptor , DR 5 , demonstrating the functional significance of Apo2L induction . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Chemotherapeutic agents upregulated expression of the Apo2L / TRAIL receptor DR 5 and the Bax homolog Bak in Baxminus sign / minus sign cells , and restored Apo2L / TRAIL sensitivity in vitro and in vivo . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
More interestingly , in vivo studies performed in SCID / nonobese diabetic mice transplanted with autologous tumor and transferred with the specific CD 4 ( + ) CTL clone in combination with IFN alpha resulted in an important APO2L / TRAIL mediated tumor growth inhibition , which was prohibited by soluble TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The most promising candidate for tumor selective death receptor activation is tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) / Apo2L , which activates the death receptors TRAIL R 1 and TRAIL R 2 , and induces apoptosis preferentially in tumor cells but not in normal tissues . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Enhancement of TRAIL / Apo2L mediated apoptosis by adriamycin through inducing DR 4 and DR 5 in renal cell carcinoma cells . ^^^ Furthermore , the synergistic cytotoxicity was significantly inhibited by DR 4 : Fc and DR 5 : Fc fusion proteins , which inhibit TRAIL / Apo2L mediated apoptosis . ^^^ These findings indicate that ADR sensitizes RCC cells to TRAIL / Apo2L mediated apoptosis through induction of DR 4 and DR 5 , suggesting that the combination therapy of TRAIL / Apo2L and ADR might be effective for RCC therapy . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Importantly , treatment of resistant cells with the chemotherapeutic agents doxorubicin , cisplatin and etoposide reversed the resistance to Apo2L / TRAIL , which was associated with drug induced upregulation of mRNA encoding the death receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Triggering cell death : the crystal structure of Apo2L / TRAIL in a complex with death receptor 5 . ^^^ Formation of a complex between Apo2L ( also called TRAIL ) and its signaling receptors , DR 4 and DR 5 , triggers apoptosis by inducing the oligomerization of intracellular death domains . ^^^ We report the crystal structure of the complex between Apo2L and the ectodomain of DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
OBJECTIVE : To explore if the antileukemic drugs Vp 16 or Ara C are able to upregulate DR 5 gene expression and enhance Apo2L induced apoptosis of HL 60 cells . ^^^ METHODS : Cell apoptosis was determined by flow cytometry after annexin V / PI staining , the effect of Apo2L on fresh leukemia cells by MTT reduction assay , the expression of DR 5 gene in HL 60 cells by semi quantitative RT PCR . ^^^ Vp 16 or Ara C upregulated DR 5 gene expression and augmented Apo2L induced apoptosis in HL 60 cells . ^^^ Ara C or Vp 16 upregulated DR 5 gene expression and increased the sensitivity of HL 60 to Apo2L induced cytotoxicity . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Apo2L / TRAIL is a homotrimeric protein that interacts with five receptors : death receptor 4 ( DR 4 ) and DR 5 mediate apoptosis activation , whereas decoy receptor 1 ( DcR 1 ) , DcR 2 , and osteoprotegerin counteract this function . ^^^ The DR 4 selective Apo2L / TRAIL variants examined in this study showed a markedly reduced ability to trigger apoptosis , whereas the DR 5 selective variants had minimally decreased or slightly increased apoptosis inducing activity . ^^^ These results suggest that DR 5 may contribute more than DR 4 to Apo2L / TRAIL induced apoptosis in cancer cells that express both death receptors . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
LLnL significantly induced the Apo2L receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Another death domain containing receptor for TRAIL ( designated as death receptor 5 ) , which preferentially engaged a FLICE ( caspase 8 ) related death protease , was also identified . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL R 2 : a novel apoptosis mediating receptor for TRAIL . ^^^ Here we report the identification of a distinct receptor for TRAIL , TRAIL R 2 , by ligand based affinity purification and subsequent molecular cloning . ^^^ TRAIL R 2 was purified independently as the only receptor for TRAIL detectable on the surface of two different human cell lines that undergo apoptosis upon stimulation with TRAIL . ^^^ TRAIL R 2 contains two extracellular cysteine rich repeats , typical for TNF receptor ( TNFR ) family members , and a cytoplasmic death domain . ^^^ TRAIL binds to recombinant cell surface expressed TRAIL R 2 , and TRAIL induced apoptosis is inhibited by a TRAIL R 2 Fc fusion protein . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Proteasome inhibitor MG 132 upregulates death receptor 5 and cooperates with Apo2L / TRAIL to induce apoptosis in Bax proficient and deficient cells . ^^^ Here , we report that proteasome inhibitor MG 132 upregulates Apo2L / TRAIL death receptor 5 expression in both Bax proficient and deficient HCT 116 cells . ^^^ These results suggest that Bax is not absolutely required for death receptor 5 dependent apoptotic signals and MG 132 by upregulating DR 5 effectively cooperates with Apo2L / TRAIL to overcome Bax deficiency induced resistance to Apo2L / TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL receptors 1 ( DR 4 ) and 2 ( DR 5 ) signal FADD dependent apoptosis and activate NF kappaB . ^^^ TRAIL induces apoptosis through two closely related receptors , TRAIL R 1 ( DR 4 ) and TRAIL R 2 ( DR 5 ) . ^^^ Here we show that TRAIL R 1 can associate with TRAIL R 2 , suggesting that TRAIL may signal through heteroreceptor signaling complexes . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
On the trail of a killer . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL is a tumor necrosis factor related ligand that induces apoptosis upon binding to its death domain containing receptors , DR 4 and DR 5 . ^^^ OPG Fc binds TRAIL with an affinity of 3 . 0 nM , which is slightly weaker than the interaction of TRID Fc or DR 5 Fc with TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Recently , a novel tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) death receptor gene , KILLER / DR5 , a member of the tumor necrosis factor receptor family , was identified as a potential mediator in p 53 dependent apoptosis and mapped to 8p21 by fluorescence in situ hybridization . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Activating TRAIL receptors DR 4 and DR 5 were expressed in all normal and malignant breast cell lines . ^^^ DR 4 , DR 5 , or TRID expression did not correlate with sensitivity to TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Interestingly , TRAIL receptor 2 but not TRAIL receptor 3 contains a cytoplasmic `` death domain ' ' necessary for induction of apoptosis and is hence designated death receptor 5 ( DR 5 ) . ^^^ In this report we describe the identification of two additional human TRAIL receptors , TRAIL receptor 2 and TRAIL receptor 3 , that belong to the tumor necrosis factor receptor family . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Two receptors for TRAIL , designated TRAIL R 2 and TRAIL R 3 , have been identified . ^^^ TRAIL R 2 is structurally similar to the death domain containing receptor TRAIL R 1 ( DR 4 ) , and is capable of inducing apoptosis . ^^^ TRAIL R 2 shows a broad tissue distribution , whereas the expression of TRAIL R 3 is restricted to peripheral blood lymphocytes ( PBLs ) and skeletal muscle . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL R 4 encodes a 386 amino acid protein with an extracellular domain showing 58 % 70 % identity to those of TRAIL R 1 , TRAIL R 2 , and TRAIL R 3 . ^^^ The signaling capacity of TRAIL R 4 is similar to that of TRAIL R 1 and TRAIL R 2 with respect to NF kappaB activation , but differs in its inability to induce apoptosis . ^^^ Like TRAIL R 1 and TRAIL R 2 , this receptor shows widespread tissue expression . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Finally , the expression of additional apoptosis inducing genes , including tumor necrosis factor receptor ( TNFR ) , FADD , TRAIL , and DR 5 , was detected in mammalian testis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The ability to transduce death signals is restricted to TRAIL R1 / TRAIL R 2 . ^^^ Constant co expression of TRAIL and of receptors TRAIL R 1 , TRAIL R 2 , and TRAIL R 3 in different tumor entities as well as in normal brain indicates that additional mechanisms might modulate the previously proposed `` decoy ' ' model . ^^^ Furthermore , in contrast to previous reports , we demonstrate TRAIL and TRAIL R 2 to be present on a transcriptional level in normal brain tissue . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Moreover , IFN stimulation caused a concomitant loss of TRAIL receptor 2 expression , which coincides with monocyte acquisition of resistance to TRAIL mediated apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Analysis by Northern blotting demonstrated mRNAs encoding TRAIL as well as the four TRAIL receptors ( DR 4 , DR 5 , DcR1 / TRID , DcR2 / TRUNDD ) in human placentas . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Two of these receptors , TRAIL R 1 and TRAIL R 2 , contain classical cytoplasmic death domains and are able to transduce an apoptotic signal . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Molecular cloning and functional analysis of the mouse homologue of the KILLER / DR5 tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) death receptor . ^^^ We report here the cloning of the mouse homologue of the TRAIL receptor KILLER / DR5 ( MK ) . ^^^ MK is highly homologous and binds TRAIL with similar affinity as human DR 4 and KILLER / DR5 . ^^^ This is the first report describing a mouse TRAIL receptor gene and also demonstrating that the p 53 dependent regulation of KILLER / DR5 mediated apoptosis is conserved between human and mouse . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Both DR 4 and DR 5 have recently been identified as membrane death receptors that are activated by their ligand TRAIL to engage the intracellular apoptotic machinery . ^^^ TRID protects from TRAIL induced apoptosis by competing with DR 4 and DR 5 for binding to TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Despite the expression of TRAIL receptors death receptor 4 and death receptor 5 , purified TRAIL could not induce programmed cell death ( PCD ) in any of the thyroid follicular cells examined . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
When used in solution , one of the anti TRAIL R 2 mAbs was capable of blocking leucine zipper human TRAIL binding to TRAIL R 2 expressing cells and prevented TRAIL induced death of these cells , whereas two of the anti TRAIL R 1 mAbs could inhibit leucine zipper human TRAIL binding to TRAIL R 1 : Fc . ^^^ Furthermore , use of the blocking anti TRAIL R 2 mAb allowed us to demonstrate that the signals transduced through either TRAIL R 1 or TRAIL R 2 were necessary and sufficient to mediate cell death . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Death receptors for FasL ( Fas ) and for TRAIL ( DR 4 , DR 5 ) are emerging as important regulators of drug induced apoptosis in human cancers , mediated by caspase activation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL , the ligand for the newly discovered DR 4 and DR 5 receptor , is a member of the TNF family of death signal transduction proteins with a mechanism of cell death similar to that of Fas and Fas ligand ( Fas L ) system . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Induction of the TRAIL receptor KILLER / DR5 in p 53 dependent apoptosis but not growth arrest . ^^^ The TRAIL death receptor KILLER / DR5 is induced by DNA damaging agents in wild type p 53 expressing cells . ^^^ Here we show that , unlike the p 53 target CDK inhibitor p21WAF1 / CIP1 , the TRAIL death receptor KILLER / DR5 is only induced in cells undergoing p 53 dependent apoptosis and not cell cycle arrest . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL , the ligand for the newly discovered DR 4 and DR 5 receptor is a member of the tumour necrosis factor ( TNF ) family of death signal tranduction proteins with a mechanism of cell death , similar to the Fas and Fas ligand ( Fas L ) system . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Yet , as popular anxieties about infectious disease have increased , public health scientists have been attracting favorable coverage in their role as `` medical detectives ' ' on the trail of the `` killer germ . ' ' . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In contrast , TRAIL expression was not induced by IL 18 , whereas it efficiently potentiated lymphokine activated killer activity of NK cells . ^^^ These results indicated preferential expression of TRAIL on IL 2 or IL 15 activated NK cells and its potential involvement in lymphokine activated killer activity . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) is a member of the TNF family that interacts with several receptors , including TRAIL R 1 , TRAIL R 2 , and TRAIL R 4 . ^^^ TRAIL R 1 and TRAIL R 2 can induce apoptosis of cancer cells and activate the transcription factor NF kappaB . ^^^ Here we show that TRAIL R 1 , TRAIL R 2 , and TRAIL R 4 induced NF kappaB activation are mediated by a TRAF 2 NIK IkappaB kinase alpha / beta signaling cascade but is MEKK 1 independent . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Structure of the TRAIL DR 5 complex reveals mechanisms conferring specificity in apoptotic initiation . ^^^ TRAIL , an apoptosis inducing ligand , has at least four cell surface receptors including the death receptor DR 5 . ^^^ Here we report the crystal structure at 2 . 2 A resolution of a complex between TRAIL and the extracellular region of DR 5 . ^^^ TRAIL forms a central homotrimer around which three DR 5 molecules bind . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The family of tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors , including the pro apoptotic DR 4 and p 53 regulated KILLER / DR5 , as well as the decoys TRID and TRUNDD , are all located on human chromosome 8p21 22 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
However , although apoptosis depends on the expression of one or both of the death domain containing receptors DR 4 and / or DR 5 , resistance to TRAIL induced apoptosis does not correlate with the expression of the `` decoy ' ' receptors . ^^^ Although DR 4 , DR 5 , DcR 1 , and OPG show similar affinities for TRAIL at 4 degrees C , their rank ordered affinities are substantially different at 37 degrees C , with DR 5 having the highest affinity ( K ( D ) < / = 2 nm ) and OPG having the weakest ( K ( D ) = 400 nm ) . ^^^ Preferentially enhanced binding of TRAIL to DR 5 was also observed at the cell surface . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
KILLER / DR5 , a tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) death receptor gene , has been shown to be induced by DNA damaging agents and radiation in a p 53 dependent manner . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL receptor 2 signals apoptosis through FADD and caspase 8 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) is a potent endogenous activator of the cell death pathway and functions by activating the cell surface death receptors 4 and 5 ( DR 4 and DR 5 ) . ^^^ This synergistic effect is p 53 dependent and may be the result of radiation induced up regulation of the TRAIL receptor DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL binds to the proapoptotic death receptors DR 4 and the p 53 regulated proapoptotic KILLER / DR5 as well as to the decoy receptors TRID and TRUNDD . ^^^ The expression level of KILLER / DR5 , TRID , TRUNDD or TRID , and TRUNDD did not correlate with TRAIL sensitivity ( P > 0 . 05 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Expression of TRAIL ( a ligand for DR 4 and DR 5 ) was significantly lower in CCSK and RTK than in normal kidney ( 9 . 5+ / 1 . 5 % 5 . 56 . 1+ / 10 . 1 % ; P = . 01 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) is a novel member of the tumor necrosis factor ( TNF ) family that induces apoptosis preferentially in tumor cells through binding to its cognate death receptors , DR 4 and DR 5 . ^^^ Exposure of such cells in vitro to soluble human TRAIL in combination with CDDP or etoposide resulted in synergistic cell death that could be blocked by soluble TRAIL neutralizing DR 5 Fc or the caspase inhibitors , Z Asp CH 2 DCB and CrmA . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
FADD is required for DR 4 and DR 5 mediated apoptosis : lack of trail induced apoptosis in FADD deficient mouse embryonic fibroblasts . ^^^ TRAIL induced apoptosis in humans is mediated by its receptors DR 4 ( TRAIL R 1 ) and DR 5 ( TRAIL R 2 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The binding analysis using the TRAIL protein and a TRAIL receptor ( death receptor 5 ) revealed that both the dimer and the trimer bind to death receptor 5 with similar affinity . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Crystal structure of TRAIL DR 5 complex identifies a critical role of the unique frame insertion in conferring recognition specificity . ^^^ We have determined the crystal structure of TRAIL in a complex with the extracellular domain of death receptor DR 5 at 2 . 2 A resolution . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The involvement of the death adaptor proteins FADD / MORT1 , TRADD , and RIP and the apoptosis initiating caspases 8 and 10 in death signaling by the two death inducing TRAIL receptors 1 and 2 ( TRAIL R 1 and TRAIL R 2 ) are controversial . ^^^ Differential precipitation of ligand stimulated TRAIL receptors demonstrated that FADD / MORT1 and caspase 8 were recruited to TRAIL R 1 and TRAIL R 2 independently of each other . ^^^ FADD / MORT1 and caspase 8 deficient Jurkat cells expressing only TRAIL R 2 were resistant to TRAIL induced apoptosis . ^^^ FADD / MORT1 and caspase 8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The tumor necrosis factor related apoptosis inducing ligand receptors TRAIL R 1 and TRAIL R 2 have distinct cross linking requirements for initiation of apoptosis and are non redundant in JNK activation . ^^^ Overexpression of the tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) receptors , TRAIL R 1 and TRAIL R 2 , induces apoptosis and activation of NF kappaB in cultured cells . ^^^ Interestingly , sTRAIL was sufficient for induction of apoptosis only in cell lines that were killed by agonistic TRAIL R 1 and TRAIL R 2 specific IgG preparations . ^^^ However , cross linking of sTRAIL was required for induction of apoptosis in cell lines that only responded to the agonistic anti TRAIL R 2 IgG . ^^^ Interestingly , activation of c Jun N terminal kinase ( JNK ) was only observed in response to either cross linked sTRAIL or anti TRAIL R 2 IgG even in cell lines where both receptors were capable of signaling apoptosis and NF kappaB activation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The TRAIL receptor KILLER / DR5 , is induced by DNA damage and appears to be regulated by the tumor suppressor gene p 53 . ^^^ While further evaluation of the role of TRAIL receptors in human cancer is ongoing , initial studies suggest that both KILLER / DR5 and DR 4 may be targets for inactivation and that these pro apooptotic receptors may be tumor suppressor genes . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RESULTS : Semiquantitative RT PCR revealed that TRAIL R 2 and TRAIL R 3 are the main TRAIL receptors used by NB cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We now show that the binding of TNF related , apoptosis inducing ligand ( TRAIL ) to its cellular receptors DR 5 ( TRAILR 2 ) and DR 4 ( TRAILR 1 ) mediates reovirus induced apoptosis . ^^^ In addition , reovirus induces both TRAIL release and an increase in the expression of DR 5 and DR 4 in infected cells . ^^^ We propose that reovirus infection promotes apoptosis via the expression of DR 5 and the release of TRAIL from infected cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
This protective effect of TRUNDD was not dependent on the presence of TRAIL , and overexpression of TRUNDD did not alter the protein levels of either p 53 or KILLER / DR 5 . ^^^ The TRAIL decoy receptor TRUNDD ( DcR 2 , TRAIL R 4 ) is induced by adenovirus p 53 overexpression and can delay TRAIL , p 53 , and KILLER / DR5 dependent colon cancer apoptosis . ^^^ We previously identified the death domain containing proapoptotic TRAIL death receptor KILLER / DR5 ( TRAIL R 2 ) as an upregulated transcript following exposure of cancer cells , with wild type but not with mutant or degraded p 53 proteins , to a cytotoxic dose of adriamycin . ^^^ In the present studies we provide evidence that expression of the TRAIL decoy receptors TRUNDD and TRID increases following infection of cancer cells with p 53 expressing adenovirus ( Ad p 53 ) , in a manner similar to other p 53 target genes such as KILLER / DR5 and p21WAF1 / CIP1 . ^^^ Further deletion studies showed that whereas protection by TRUNDD against TRAIL mediated apoptosis did not require an intact intracellular domain ( ICD ) , the first 43 amino acids of the ICD of TRUNDD were needed for protection against cell death induced by p 53 or KILLER / DR5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
It is regulated by 2 death receptors , TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL R 2 , and 2 decoy receptors , TRAIL R 3 and TRAIL R 4 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Whereas both S and N type cell lines express TRAIL R 2 , FADD , and caspase 3 and 10 , only S type cells express caspase 8 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
However , all DC populations expressed CD 95 , TRAIL R 2 , and TRAIL R 3 at comparable levels , suggesting that sensitivity to death ligand induced DC apoptosis is not regulated at the receptor level . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Because CD 437 induced the expression of DR 4 , DR 5 and Fas , we examined the effects of combining CD 437 and tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) and Fas ligand , respectively , in HPC cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL sensitivity of the PNET cell lines was correlated with mRNA expression levels of TRAIL , its agonistic ( TRAIL R 1 , TRAIL R 2 ) and antagonistic ( TRAIL R 3 , TRAIL R 4 ) receptors , cellular FLICE like inhibitory protein ( cFLIP ) , caspase 3 and caspase 8 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RESULTS : Although both S and N type cell lines express TRAIL R 2 , FADD , and caspases 3 and 10 , only S type cells express caspase 8 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Flow cytometric analysis revealed cell surface expression of TRAIL R 1 and TRAIL R 2 on PancTuI and Colo 357 , and TRAIL R 2 on Panc 1 cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we report that TRAIL is constitutively expressed on murine natural killer ( NK ) cells in the liver and plays a substantial role in suppressing tumor metastasis . ^^^ Freshly isolated NK cells , but not natural killer T cells or ordinary T cells , from the liver expressed cell surface TRAIL , which was responsible for spontaneous cytotoxicity against TRAIL sensitive tumor cells in vitro along with perforin and Fas ligand ( FasL ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we demonstrate that all RCC cell lines express TRAIL as well as the death inducing receptors TRAIL R 1 ( DR 4 ) and TRAIL R 2 ( Killer / DR5 ) . ^^^ Topotecan , a novel topoisomerase 1 inhibitor , induced upregulation of TRAIL R 2 as well as downregulation of TRAIL . ^^^ Neutralization of TRAIL with recombinant soluble TRAIL R 1 Fc and TRAIL R 2 Fc failed to inhibit topotecan induced apoptosis indicating that topotecan induced cell death can occur in a TRAIL independent fashion . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
KILLER / DR5 TRAIL receptor expression by glucocorticoids and interferon gamma . ^^^ KILLER / DR5 is a death domain containing proapoptotic receptor that binds to the cytotoxic ligand TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induces apoptosis via the death receptors DR 4 and DR 5 in different transformed cells in vitro and exhibits potent antitumor activity in vivo with minor side effects . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL triggers apoptosis by binding to its two proapoptotic receptors DR 4 and DR 5 , a process which is negatively regulated by binding of TRAIL to its two decoy receptors TRID and TRUNDD . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
To investigate the therapeutic potential of TRAIL , we analyzed the expression of TRAIL and its apoptosis inducing receptors ( DR 4 and DR 5 ) in the normal and cancerous human pancreas , and the sensitivity of pancreatic cancer cells to TRAIL cytotoxicity . ^^^ TRAIL , DR 4 and DR 5 mRNA levels were concomitantly increased in pancreatic cancers compared with normal controls ( P < 0 . 01 ) , and there were positive correlations between the expression levels of TRAIL and DR 4 , TRAIL and DR 5 and between DR 4 and DR 5 mRNA ( r=0 . 85 , r=0 . 87 , r=0 . 91 ; P < 0 . 01 ) . ^^^ In five pancreatic cancer cell lines , TRAIL , DR 4 and DR 5 mRNA expression was detectable at various levels . ^^^ However , independent of the presence of DR 4 and DR 5 , TRAIL cytotoxicity assays revealed that pancreatic cancer cells showed a significantly lower sensitivity ( LD ( 50 ) > 85 ng / ml ) to TRAIL treatment than Jurkat T lymphoma cells ( LD ( 50 ) =7 . 2 ng / ml ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Recently , it was shown that the expression of TRAIL R 2 , also known as KILLER , Trick or DR 5 , can be induced by either DNA damage or overexpression of a wild type p 53 transgene , suggesting a role for p 53 in the death signaling pathway . ^^^ TRAIL R 2 is not correlated with p 53 status and is rarely mutated in non small cell lung cancer . ^^^ Furthermore , mutations in the death domain of TRAIL R 2 were reported in 10 . 6 % of non small cell lung cancer ( NSCLC ) patients in a Korean population , suggesting a role for TRAIL R 2 in lung tumorigenesis . ^^^ MATERIALS AND METHODS : To determine the association between expression of TRAIL R 2 and p 53 mutation status in lung cancers , we compared the two events in 20 small cell lung cancer ( SCLC ) cell lines , 20 NSCLC cell lines , and 30 primary NSCLC tumors . ^^^ We also sequenced the death domain of TRAIL R 2 in a total of 100 primary NSCLC . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Susceptibility of the prostate cancer cell types to Apo 2L / TRAIL induced apoptosis did not appear to correlate with the levels of the Apo 2L / TRAIL receptors death receptor ( DR ) 4 ( TRAIL receptor 1 ) or DR 5 ( TRAIL receptor 2 ) , decoy receptor ( DcR ) 1 and DcR 2 , Flame 1 , or the inhibitors of apoptosis proteins family of proteins . ^^^ Treatment with paclitaxel or taxotere increased DR 4 and / or DR 5 protein levels ( up to 8 fold ) without affecting the protein levels of DcR 1 and DcR 2 , Apo 2L / TRAIL , Fas , or Fas ligand . ^^^ These findings indicate that up regulation of DR 4 and DR 5 protein levels by treatment with paclitaxel enhances subsequent Apo 2L / TRAIL induced apoptosis of human prostate cancer cells . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Both sensitive and resistant cell lines expressed TRAIL death receptor ( DR 5 ) , adapter protein Fas associated death domain ( FADD ) , and caspase 8 ; but resistant cell lines expressed 2 fold higher levels of the apoptosis inhibitor phosphoprotein enriched in diabetes / phosphoprotein enriched in astrocytes 15 kDa ( PED / PEA 15 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor ( TNF ) alpha related apoptosis inducing ligand ( Apo 2L / TRAIL ) , after binding with its signaling death receptors ( DR 4 and DR 5 ) , triggers the intrinsic `` mitochondrial ' ' pathway of apoptosis more efficiently in the cancer than do normal cells . ^^^ Reduced effects of Apo 2L / TRAIL in Bcr Abl positive leukemic cells were not attributable to diminished expression of DR 4 and DR 5 , or higher expressions of the decoy receptors DcR 1 and 2 or c FLIP ( L ) . ^^^ Cotreatment with STI 571 significantly enhanced Apo 2L / TRAIL induced apoptosis ( P < 0 . 01 ) as well as increased the processing of caspase 9 and 3 and XIAP , without affecting the levels of DR 4 , DR 5 , decoy receptors , or c FLIP ( L ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) contributes to interferon gamma dependent natural killer cell protection from tumor metastasis . ^^^ Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) is expressed by in vitro activated natural killer ( NK ) cells , but the relevance of this observation to the biological function of NK cells has been unclear . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL induces apoptosis via death receptors ( DR 4 and DR 5 ) in a wide variety of tumor cells but not in normal cells . ^^^ These data suggest that death receptors ( DR 4 and DR 5 ) and Fas receptors induced apoptosis through identical signaling pathway , and TRAIL induced apoptosis via both mitochondrial dependent and independent pathways . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Although three other TRAIL receptors DR 5 , DcR 1 , and DcR 2 are induced by DNA damage and are regulated by the wild type p 53 tumor suppressor , it was not known whether these factors also affect DR 4 expression . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL ( tumor necrosis factor ( TNF ) related apoptosis inducing ligand ) , a recently identified member of the growing TNF superfamily , binds to its cognate `` death ' ' receptors DR 4 and DR 5 as well as `` decoy ' ' receptors DcR 1 and DcR 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL / PSI did not affect the level of mRNA expression for TRAIL receptors ( DR 4 , DR 5 , DcR 1 ) and other apoptosis signal transduction molecules ( TRADD , caspase 8 ) . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
These alterations result in amino acid changes in or near the ligand binding domain of DR 4 and , based on the crystal structure of DR 5 and its homology with DR 4 , have the potential to affect TRAIL binding to DR 4 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL binds to death receptors ( DRs ) DR 4 , DR 5 , DcR 1 , and DcR 2 . ^^^ We found that 9 of 10 ESFT cell lines expressed both DR 4 and DR 5 by Western blotting , whereas the TRAIL resistant line expressed only DR 4 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
It is well known that TRAIL binds to the death signaling receptors , DR 4 and DR 5 , and initiates the TRAIL death pathway . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Four related receptors bind TRAIL , two death receptors ( DR 4 and DR 5 ) that signal apoptosis and two decoy receptors ( DcR 1 and DcR 2 ) that act as dominant negative inhibitors of TRAIL mediated apoptosis . ^^^ Our results indicate that overexpression of cRel or activation of endogenous Rel / NF kappaB factors by TNFalpha in HeLa cells up regulates DcR 1 without changing the expression of DcR 2 , DR 4 , and DR 5 and makes cells resistant against TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
However , it did not change the mRNA expression level of death mediating TRAIL receptors , e . g . , DR 4 and DR 5 , which were constitutively expressed in both cell lines . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The levels of both TRAIL R 1 and TRAIL R 2 , low in Daudi cells , were enhanced by IFN alpha . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Trail , a tumor necrosis factor related apoptosis inducing ligand , is a novel potent endogenous activator of the cell death pathway through the activation of cell surface death receptors Trail R 1 and Trail R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL R 2 expression predicted sensitivity to apoptosis . ^^^ Drug exposure resulted in enhanced TRAIL R 2 expression , but decreased TRAIL R 4 expression in U87MG cells . ^^^ Ectopic expression of dominant negative p 53 ( V135A ) abrogated the drug induced changes in TRAIL R 2 and TRAIL R 4 expression , but had no effect on synergy . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The co crystal structure of TRAIL with one of its signalling receptors TRAILR 2 has been solved , opening the way to rational small molecule drug design . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Dox up regulated the expression of the TRAIL receptor death receptor 5 ( DR 5 ) and synergistically enhanced the effect of TRAIL not only against MM cells sensitive to , but also against those resistant to , Dex or Dox induced apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In addition , TRAIL and chemotherapy can act cooperatively , possibly as a result of chemotherapy induced increases in expression of a TRAIL receptor , DR 5 . ^^^ We used cell lines derived from a highly chemoresistant tumor , malignant mesothelioma , to learn whether TRAIL was effective alone or together with chemotherapy and whether cooperativity depended on increases in DR 5 expression . ^^^ We conclude that TRAIL and chemotherapy act cooperatively to kill mesothelioma cell lines , not by increases in DR 5 receptor but in association with mitochondrial amplification of apoptotic signals . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
A novel anti human DR 5 monoclonal antibody , TRA 8 , induces apoptosis of most tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) sensitive tumor cells both in vitro and in vivo . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Furthermore both c FLIP ( S ) and Bcl XL protected against overexpression of the TRAIL receptors DR 4 and KILLER / DR5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The TRAIL mechanism induced 2 APO was blocked by the caspase 6 inhibitor , VEID , and by the soluble fusion proteins , DR 4 or DR 5 , which act as decoy receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Differential activation of TRAIL R 1 and 2 by soluble and membrane TRAIL allows selective surface antigen directed activation of TRAIL R 2 by a soluble TRAIL derivative . ^^^ Using antagonistic antigen binding fragment ( Fab ) preparations of TRAIL R 1 and TRAIL R 2 specific antibodies , we demonstrate in this study that TRAIL R 1 becomes activated by both the soluble and the membrane bound form of the ligand , whereas TRAIL R 2 becomes only activated by memTRAIL or soluble TRAIL secondarily cross linked by antibodies . ^^^ Furthermore , we show that the restricted signal capacity of sTRAIL can be readily converted into a fully signal competent memTRAIL like molecule , i . e . a TRAIL R 2 stimulating ligand , by genetic fusion to an antibody derivative that allows antigen dependent ' immobilization ' of the fusion protein to cell surfaces . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) induces apoptosis through two receptors , TRAIL R 1 ( also known as death receptor 4 ) and TRAIL R 2 ( also known as death receptor 5 ) , that are members of the TNF receptor superfamily of death domain containing receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
On the trail of a killer . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
No changes in the expressions of TRAIL receptors ( DR 4 and DR 5 ) and Bcl 2 or Bax were found after treatment . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RESULTS : We detected the expression of the receptors Fas , TRAMP , TRAIL R 2 and TRAIL R 3 in hLECs . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In previous studies we have shown that the sensitivity of melanoma cell lines to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induced apoptosis was determined largely by the level of expression of death receptor TRAIL receptor 2 on the cells . ^^^ However , approximately one third of melanoma cell lines were resistant to TRAIL , despite expression of high levels of TRAIL receptor 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
By contrast , HHV 7 infection caused a marked decrease of surface TRAIL R 1 , but not of TRAIL R 2 , CD 95 , TNF R 1 , or TNF R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , a member of the tumor necrosis factor ( TNF ) family , binds to several cell surface receptors with distinct functions ( agonistic receptors 1 and 2 [ TRAIL R 1 , TRAIL R 2 ] ; decoy receptors 3 and 4 [ TRAIL R 3 , TRAIL R 4 ] ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
AZT and IFN alpha mediated apoptosis in PEL was blocked by stable overexpression of dominant negative Fas Associated Death Domain ( FADD ) , decoy receptor 2 ( DcR 2 ) , soluble TRAIL receptor fusion proteins ( DR 4 and DR 5 ) and thymidine . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Antiviral response by natural killer cells through TRAIL gene induction by IFN alpha / beta . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Adriamycin treatment modestly up regulated Apo2L / TRAIL R 2 ( DR 5 ) and had no effect on the expression of Fas associated death domain , c FLIP , Bcl 2 , Bcl ( xL ) , Bax , and IAP family members ( cIAP 1 , cIAP 2 , XIAP , and survivin ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
These uPAR deficient transfected cells had higher levels of the TRAIL receptors DR 4 and DR 5 than did the control and vector population as detected by flow cytometry . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
DAP 3 also associates with the pro caspase 8 binding adapter protein Fas associated death domain ( FADD ) , and links FADD to the TRAIL receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
These studies demonstrated that doxorubicin , an agent which is commonly used to treat MM patients , upregulated the expression of the DR 5 death signalling TRAIL receptor and synergistically enhanced the pro apoptotic effect of TRAIL on MM cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In this study , we investigated whether the TRAIL DR 5 system transduces signals similar to those induced by other TNF family ligands and receptors . ^^^ To address this issue , two human glioma cell lines , CRT MG and U 87 MG , were used , and an agonistic antibody against DR 5 ( TRA 8 ) and human recombinant TRAIL were used to ligate DR 5 . ^^^ We demonstrate that DR 5 ligation by either TRAIL or TRA 8 induces two functional outcomes , apoptosis and expression of the chemokine interleukin 8 ( IL 8 ) ; the nonspecific caspase inhibitor Boc D Fmk blocks both TRAIL mediated cell death and IL 8 production ; the caspase 3 specific inhibitor z DEVD Fmk suppresses TRAIL mediated apoptosis but not IL 8 induction ; caspase 1 and 8 specific inhibitors block both TRAIL mediated cell death and IL 8 production ; and DR 5 ligation by TRAIL mediates AP 1 and NF kappaB activation , which can be inhibited by caspase 1 and 8 specific inhibitors . ^^^ Therefore , the TRAIL DR 5 system has a role not only as an inducer of apoptotic cell death but also as a transducer for proinflammatory and angiogenic signals in human brain tumors . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL , FasL and a blocking anti DR 5 antibody augment paclitaxel induced apoptosis in human non small cell lung cancer . ^^^ Fas and Trail receptors ( DR 4 and DR 5 ) are TNF family members and act as death signal transduction proteins in the apoptosis cascade . ^^^ Despite the importance of PA in lung cancer treatment , the function of Fas , DR 4 and DR 5 in PA induced apoptosis , as well as the effect of their respective ligands FasL and TRAIL alone or in combination with PA , remains poorly understood . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We demonstrate that in H 157 human lung carcinoma cells , etoposide and doxorubicin induce the NF kappaB dependent expression of both pro and anti apoptotic proteins including TRAIL and its death receptor , DR 5 , and IAPs . ^^^ Inhibition of NF kappaB activation in H 157 cells in response to genotoxin resulted in loss of cell surface expression of TRAIL and DR 5 , aggressive growth and chemotherapy resistance of tumors in nude mice . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Data from immunoblotting analysis reveal that glucose deprivation enhanced TRAIL cytotoxicity is inversely related to the intracellular level of FLICE inhibitory protein ( FLIP ) but not that of death receptor 5 ( DR 5 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Upon binding of tumour necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) , the agonistic TRAIL receptors DR 4 and DR 5 activate caspase 8 leading to apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
IFN gamma or TRAIL treatment alone did not change expression of other pro or antiapoptotic proteins such as DR 4 , DR 5 , FADD , Bax , IAP 1 , XIAP , Bcl 2 , and Bcl XL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
This regulation of TRAIL mediated apoptosis by inflammatory cytokines appears to be due to alterations of cell surface expression of TRAIL receptor DR 5 and not DR 4 . ^^^ We also show the in vivo presence of TRAIL and TRAIL receptors DR 5 and DcR 1 in both normal and inflamed thyroids . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
BACKGROUND & AIMS : Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) is a member of the tumor necrosis factor family and induces apoptosis by cross linking either of the 2 TRAIL receptors containing a death domain ( TRAIL R 1 or TRAIL R 2 ) . ^^^ RESULTS : Normal colonic epithelial cells express TRAIL , TRAIL R 1 , TRAIL R 2 , and TRAIL R 4 . ^^^ Interestingly , TRAIL and TRAIL R 2 are coexpressed mostly in the luminal surface epithelium . ^^^ Using an infection model with restricted human cytomegalovirus gene expression or productive adenovirus infection in the colon carcinoma cell line Caco 2 , we show that TRAIL sensitivity of colonic epithelial cells is induced on virus infection along with an up regulation of TRAIL R 1 and TRAIL R 2 on the cell surface . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We found that HL 60 cells , which express TRAIL receptors ( also called death receptor , DR ) DR 4 , DR 5 , and Dc ( decoy ) R 2 , are highly sensitive to TRAIL induced cytotoxicity . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL can bind to four different receptors , two pro apoptotic death receptors ( DRs ) , DR 4 and DR 5 , and two antiapoptotic decoy receptors ( DcRs ) , DcR 1 and DcR 2 . ^^^ We studied the tumor specific down regulation of the TRAIL receptors DcR 1 and DcR 2 , as well as DR 4 and DR 5 , in a group of pediatric tumor cell lines [ nine neuroblastoma and three peripheral primitive neuro ectodermal tumors ( PNETs ) ] and three cell lines from adult tumors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumour necrosis factor related apoptosis inducing ligand ( TRAIL / APO 2L ) induces apoptosis in a variety of tumour cells upon binding to death receptors TRAIL R 1 and TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Among T cells , CEM underwent apoptosis in response to CH 11 but were resistant to Trail in agreement with the absence of Trail receptors ( DR 4 and DR 5 ) on their surface . ^^^ As B cell lines expressed significant levels of DR 4 and DR 5 , resistance to Trail in SKW 6 . 4 is likely due to the expression of the decoy receptor DcR 1 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
FasL and TRAIL are apoptotic ligands of the TNF like cytokines family , acting via activation of the transmembrane death domain containing receptors Fas for FasL , and DR 4 or DR 5 for TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
METHODS : We investigated the presence and functional status of TRAIL and its receptors , DR 4 , DR 5 , and DcR 2 on tumor as well as tumor infiltrating lymphocytes ( TIL ) in primary ( n=37 ) , and metastatic gastric carcinoma from malignant ascites ( n=37 ) by a flow cytometry . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RESULTS : For RPE cells derived directly from the eye , we detected mRNAs of Trail R 2 , Trail R 3 , TRAIL , and APO 3 L , but not Trail R 1 , Trail R 4 , and TRAMP . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL binds four different membrane bound receptors : DR 4 , DR 5 , DcR 1 , and DcR 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Sensitization of PSC with culture duration was accompanied by increased expression of CD 95 and TRAIL receptor 2 and no alterations of Flip expression or protein kinase B phosphorylation but was paralleled by the appearance of a COOH terminal cleavage product of receptor interacting protein . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Combination of CP 31398 and TRAIL or chemotherapeutic agents enhanced cancer cell killing effect possibly through upregulation of p 53 regulated genes such as KILLER / DR5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TG selectively upregulated DR 5 but had no effect on the expression of the other TRAIL receptor , DR 4 . ^^^ TG also upregulated the expression of the DR 5 ligand TRAIL ( tumor necrosis factor related apoptosis inducing ligand ) , albeit in a cell type specific manner . ^^^ We found that TG upregulation of DR 5 and TRAIL was coupled with caspase 8 activation and Bid cleavage , suggesting that the TG regulated DR 5 pathway could be linked to the mitochondrial pathway . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
It is regulated by 2 death receptors , TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL R 2 and 2 decoy receptors , TRAIL R 3 and TRAIL R 4 . ^^^ In HCC cell lines , their TRAIL resistance did not correlate with the basal expression level of TRAIL receptors or c FLIP , however , in human tissues , TRAIL R 1 and TRAIL R 2 expressions were notably decreased compared to normal counterpart . ^^^ These results suggest that ( a ) the majority of human HCC cell lines are resistant to TRAIL induced apoptosis and cycloheximide sensitive short lived antiapoptotic molecule ( s ) is responsible for this resistance , ( b ) the expression of TRAIL R 1 and TRAIL R 2 is reduced in HCC tissues , and the increased expression of TRAIL R 1 may be a mechanism of cisplatininduced sensitization to TRAIL induced apoptosis in some HCC cells , and ( c ) the activation of NF kappaB may not be involved in the TRAIL resistance of HCC cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We determined whether forced COX 2 expression modulates apoptosis induction by tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , a member of tumor necrosis factor ligand family , and examined determinants of the apoptotic pathway , including membrane death receptors ( DR 4 and DR 5 ) . ^^^ Forced COX 2 expression significantly attenuated TRAIL induced apoptosis and was associated with transcriptional repression of DR 5 and up regulation of Bcl 2 . ^^^ Sulindac sulfide treatment restored DR 5 expression and , when combined with TRAIL , reduced cell viability to a greater extent than did either drug alone . ^^^ In summary , modulation of DR 5 and Bcl 2 levels by COX 2 attenuates TRAIL induced apoptosis and represents a novel mechanism of intrinsic drug resistance in human colon cancer cells . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induced apoptosis is mediated by its receptors DR 4 ( TRAIL R 1 ) and DR 5 ( TRAIL R 2 ) and the adapter protein Fas associated death domain protein ( FADD ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Low levels of the death inducing TRAIL receptors , TRAIL R 1 and TRAIL R 2 but not the putative ' decoy ' receptors , TRAIL R 3 and TRAIL R 4 , were expressed on the surface of B CLL cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Cytoplasmic and cell surface expression of the TRAIL receptors DR 4 and DR 5 was observed in this patient ' s tumor by immunohistochemistry . ^^^ Tumors treated with CPT 11 showed increased membrane expression of DR 5 , suggesting that CPT 11 may increase sensitivity to TRAIL by up regulation of DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) up regulates death receptor 5 ( DR 5 ) mediated by NFkappaB activation in epithelial derived cell lines . ^^^ This activation is regulated by the recruitment of an adaptor protein Fas associating death domain ( FADD ) to TRAIL death receptors , death receptor 4 ( DR 4 , TRAIL R 1 ) and death receptor 5 ( DR 5 TRAIL R 2 ) . ^^^ Herein we demonstrate that TRAIL increases expression of DR 5 in human embryonic kidney ( HEK ) 293 , MCF 7 and MDA MB 231 epithelial cell lines while DR 4 expression remains unchanged . ^^^ Blockage of NFkappaB activation either by expression of dominant negative IkappaB or treatment with proteasome inhibitor lactacystin eliminates TRAIL induced DR 5 expression . ^^^ Thus , TRAIL mediated NFkappaB activation increases DR 5 expression thereby amplifying the apoptotic response of TRAIL in epithelial derived cells . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The adenovirus encoded receptor internalization and degradation ( RID ) protein ( previously named E 3 10 . 4K / 14 . 5K ) , which is composed of RIDalpha and RIDbeta subunits , down regulates a number of cell surface receptors in the tumor necrosis factor ( TNF ) receptor superfamily , namely Fas , TRAIL receptor 1 , and TRAIL receptor 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
MATERIAL / METHODS : To test this hypothesis , we estimated by FACS analysis the turnover rates of receptors for TRAIL ( TRAILR 1 and TRAILR 2 ) , signal regulatory protein SIRPa , receptor for alpha / beta interferon ( INFR 1 ) , and poliovirus receptor ( CD 155 ) on the surface of HeLa cells after the treatment with brefeldin A ( to stop receptor replenishment through the Golgi mediated trafficking ) or poliovirus infection . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL interacts with four receptors : two signalling receptors ( TRAIL R 1 and TRAIL R 2 ) and two decoy receptors ( TRAIL R 3 and TRAIL R 4 ) . ^^^ A blocking experiment with monoclonal antibodies directed against TRAIL R 1 and TRAIL R 2 revealed that TRAIL R 1 is mainly involved in TRAIL induced apoptosis of ahOL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we demonstrate that the expression of both TRAIL / Apo 2 ligand and the death receptors ( DR ) DR 5 and DR 4 , but not Fas , are sustained in IL 6 differentiated Ig secreting human plasma cells as well as primary mouse plasma cells generated in a T dependent immune response . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
To evaluate the involvement of TRAIL receptors in breast carcinogenesis , we have analyzed the entire coding region of TRAIL R 2 and the death domain ( DD ) regions of TRAIL R 1 and R 4 for the detection of somatic mutations in a series of breast tumors , lymph node metastases and BC cell lines . ^^^ Additionally , we analyzed individuals from BC families for the detection of TRAIL R 2 germline mutations . ^^^ In BC cell lines , a strongly decreased mRNA expression of TRAIL , TRAIL R 1 , R 3 and R 4 was found , whereas the expression of TRAIL R 2 was only slightly reduced . ^^^ No correlation was found between the expression level of TRAIL and the receptor mRNAs and clinicopathologic variables and between the expression of TRAIL R 2 and TP 53 mutation status and loss of heterozygosity ( LOH ) at 8p21 p 22 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
This was confirmed by quantitative immunocytochemical image analysis of BAL eosinophils and alveolar macrophages , which demonstrated that expression levels of TRAIL and DcR 2 increased , whereas expression levels of the TRAIL Rs DR 4 and DR 5 decreased in asthmatic subjects after SAC . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Immunotherapies to replace the defective cytokines or to restore a potentially defective DC T lymphocyte feed back might help patients restore their immune responses under antiviral therapy . ( 2 ) After measles and other viral infections , or incubation with dsRNA , DCs become cytotoxic and consequently exhibit natural killer function , through upregulation of type 1 IFN secretion which enhances TRAIL expression . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Because CASP 8 is a key component of the death inducing signaling complex ( DISC ) when specific death receptors ( including DR 4 , DR 5 , FAS ) are activated by their specific ligands ( TRAIL / FASL ) , we examined expression of the components of the DISC complex in lung cancer cell lines . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL receptor ( TRAIL R ) 1 and TRAIL R 2 , but not TRAIL R 3 and TRAIL R 4 , mediate apoptosis . ^^^ RESULTS : In normal colon mucosa , TRAIL and TRAIL R 2 were expressed mostly in the surface epithelium , whereas TRAIL R 1 and TRAIL R 4 were detected all along the crypt axis . ^^^ TRAIL , TRAIL R 2 , TRAIL R 3 , and TRAIL R 4 expression did not correlate statistically with disease free survival ( multivariate analysis : P = 0 . 54 , P = 0 . 67 , P = 0 . 45 , and P = 0 . 69 , respectively ) , but TRAIL R 1 expression was significantly associated with disease free survival in colon cancer ( multivariate analysis : P = 0 . 003 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Using mouse models of adenoviral hepatitis and livers of patients with hepatitis infection , we could demonstrate that apoptosis in virally infected hepatocytes is mediated by TRAIL receptor DR 5 and TRAIL . ^^^ Overexpression of TRAIL in the liver after viral infection is not dependent on lymphocytes , natural killer , or Kupffer cells , which indicates that the TRAIL receptor / ligand system is a paracrine mechanism of hepatocytes against virally infected cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Many cancer cell lines preferentially express TRAIL R 1 and TRAIL R 2 , suggesting differential regulation of the death and decoy receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL receptor mRNAs ( DR 4 , DR 5 , and DcR 2 ) were induced by doxorubicin but these changes were not reflected at the protein level . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The sensitivity to TRAIL was correlated with cell surface expression of death inducing receptors DR 4 and / or DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In patients with severe lymphocytic sialadenitis , TRAIL R 1 , TRAIL R 2 , or both were strongly expressed on the ductal epithelial cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Somatic mutations of TRAIL R 1 and TRAIL R 2 genes may play a role in the pathogenesis of some tumors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Recent reports have suggested that the death ligand tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) may partially limit the formation of hepatic metastases of a variety of mouse tumors , and the major source of TRAIL in the liver was shown to be local natural killer cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We identified the presence of mRNAs for TRAIL , TRAIL R 2 , and TRAIL R 3 , and cell surface expression of TRAIL R 2 and R 3 in neutrophil populations . ^^^ Using blocking Abs to TRAIL receptors , specifically TRAIL R 2 , and a TRAIL R 1 : FcR fusion protein , we have excluded a role for TRAIL in regulating constitutive neutrophil apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
AIM : To observe the localization of TRAIL / TRAIR ( DR 4 , DR 5 , DcR 1 , DcR 2 ) in the fetal pancreas . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
This study shows that 2ME2 uses the extrinsic pathway for induction of apoptosis . 2ME2 treatment results in up regulation of death receptor 5 ( DR 5 ) protein expression in vitro and in vivo and renders cells more sensitive to the cytotoxic activities of the DR 5 ligand tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . 2ME2 induced apoptosis requires caspase activation and kinetic studies show the sequential activation of caspase 8 , caspase 9 , and caspase 3 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
However , when RT PCR was performed with mRNA from the PBLs of five individuals , only four genes , including TRAIL receptor 2 , DRAL ( now known as FHL 2 ) , cyclin G , and cyclin protein gene , showed greater than 50 % agreement between gene induction as detected by microarray analysis and by RT PCR . ^^^ These results suggested that the relative expression levels of genes such as TRAIL receptor 2 , FHL 2 , cyclin G , and cyclin protein gene in PBLs may provide estimates of radiation exposures . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We show that genotoxic agents such as cisplatin , doxorubicin and camptothecin , in addition to UV radiation , can induce TRAIL R 2 on the cell surface of TRAIL receptor negative tumour cells . ^^^ Newly synthesised TRAIL R 2 is functional , so apoptosis is effectively induced by TRAIL , but it is significantly inhibited by constitutive expression of dominant negative p 53 . ^^^ In addition , apoptosis induced by pretreatment of genotoxic agents and additional stimulation of TRAIL is efficiently inhibited by either antagonistic anti TRAIL R 2 antibody or pan caspase inhibitor z VAD FMK . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Apo 2L / TRAIL ( tumor necrosis factor related apoptosis inducing ligand ) is a member of the tumor necrosis factor superfamily and has recently been shown to induce apoptosis through engagement of the death receptors TRAIL R 1 ( DR 4 ) and TRAIL R 2 ( DR 5 ) . ^^^ Overexpression of a transdominant negative mutant of the inhibitory protein 1 kappa B alpha results in down regulation of constitutively active NF kappa B , induction of DR 5 , and tumor necrosis factor receptor ( TNFR ) 1 associated death domain expression and enhancement of TRAIL sensitivity . ^^^ Overexpression of RelA subunit inhibits caspase 8 and DR 4 and DR 5 expression and enhances expression of cIAP 1 and c IAP 2 after TRAIL treatment . ^^^ By comparison , overexpression of c Rel enhances DR 4 , DR 5 , and Bcl 10 ( s ) and inhibits cIAP 1 , cIAP 2 , and survivin after TRAIL treatment . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Interferon alpha sensitizes human hepatoma cells to TRAIL induced apoptosis through DR 5 upregulation and NF kappa B inactivation . ^^^ IFN alpha pretreatment enhanced TRAIL induced apoptosis of HuH 7 and Hep3B cells , in which IFN alpha upregulated the expression of DR 5 , a death receptor of TRAIL , and downregulated the expression of survivin , which has an antiapoptotic function . ^^^ In contrast , IFN alpha did not enhance TRAIL induced apoptosis of HepG 2 cells , in which expression of DR 5 and survivin was not affected by IFN alpha . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Apoptosis assays and Western blot analyses revealed that apoptosis resistance to TRAIL correlates well with the level of Akt phosphorylation at Ser 473 rather than protein expression levels of TRAIL receptors , DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Abnormalities of various components of these pathways have been identified in human cancer including loss of FAS expression , deletion or loss of TRAIL receptor DR 4 , mutation of TRAIL receptor DR 5 , overexpression of TRAIL decoy TRID or overexpression of Fas decoy , as well as overexpression of the caspase activation inhibitor , FLIP . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Eight human DRs ( Fas , TNF R 1 , TRAMP , TRAIL R 1 , TRAIL R 2 , DR 6 , EDA R and NGF R ) have been identified . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Using two agonistic monoclonal antibodies specific for each death receptor of TRAIL , 2E12 ( anti human DR 4 ) and TRA 8 ( anti human DR 5 ) , we examined the signal transduction of the death receptors in combination with or without chemotherapy agents such as Adriamycin ( doxorubicin hydrochloride ) and Cisplatin . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Natural Killer ( NK ) cells can induce apoptosis in target cells in at least four ways : by secretion of granzyme B / perforin ( GrB / P ) and via the CD95L , TRAIL and TNF alpha pathways . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
This resistance was determined by failure to form the TRAIL DISC and by decreased TRAIL R 1 and TRAIL R 2 levels after androgen deprivation ; the capacity of TRAIL to induce DISC formation was completely restored in the presence of DHT . ^^^ Surprisingly , we found that wortmannin decreased the total amount of TRAIL R 1 , but not TRAIL R 2 , in the cells as well as the amount of TRAIL R 1 precipitated by TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
When Colo 205 cells were cultured with 50 % CM A , cell surface expression of TRAIL death receptors DR 5 and DR 4 increased 13 fold and sixfold , respectively , compared with that of untreated Colo 205 cells . ^^^ CONCLUSION : Macrophages from cancer patients appear to be activated by tumor cells to produce TRAIL and to increase the expression of TRAIL death receptors DR 4 and DR 5 on tumor cells . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We found that most TRAIL resistant and partial resistant clones expressed low levels of DR 5 , whereas most TRAIL sensitive clones expressed high levels of Death Receptor ( DR 5 ) . ^^^ However , there were clones with a range of different TRAIL sensitivities that had similar levels of DR 5 expression . ^^^ Our results showed that the expression levels of DR 5 , the activation levels of caspase 8 , 3 and RIP were critical factors in determining TRAIL sensitivities in Jurkat cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL R 2 , R 3 , R 4 and osteoprotegerin ( OPG ) expression did not correlate with TRAIL sensitivity . ^^^ Coincubation of TRAIL and doxorubicin led to the overexpression of TRAIL R 2 resulting in a synergistic effect of doxorubicin and TRAIL in TRAIL sensitive cell lines and in the overcoming of TRAIL resistance in all of the TRAIL resistant cell lines , except HTB 91 , which lacked caspase 8 expression . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In epithelial cells , reovirus induced apoptosis involves the release of tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) from infected cells and the activation of TRAIL associated death receptors ( DRs ) DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we demonstrate that all RCC cell lines coexpress TRAIL and the death inducing receptors , TRAIL R 1 and TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
To determine the molecular mechanisms involved in the enhanced apoptosis , we examined the expression of two TRAIL death receptors ( DR 4 and DR 5 ) and two TRAIL decoy receptors ( DcR 1 and DcR 2 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
PMA also increased the expression of TRAIL receptors DR 4 and DR 5 ; this expression was inhibited by the PKC inhibitors GF109203x , G6983 , and Ro 31 8220 and the MEK inhibitor UO 126 , suggesting a role for conventional PKC isoforms and MEK in the regulation of TRAIL receptor expression . ^^^ CONCLUSIONS : PKC stimulation in PANC 1 cells increases expression of the pro apoptotic gene Bad and the TRAIL receptors , DR 4 and DR 5 , through both conventional PKC and MEK dependent pathways . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TLCS induced CD 95 and TRAIL receptor 2 trafficking to the plasma membrane were significantly inhibited . ^^^ Blockade of protein kinase A ( PKA ) abolished the inhibitory effect of cAMP on TLCS induced CD 95 membrane targeting , but not TRAIL receptor 2 membrane targeting , PKB and MAP kinase responses . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The SK N MC neuroblastoma cell line , which expresses surface tumour necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors TRAIL R 2 and TRAIL R 4 , was used as a model system to examine the effect of TRAIL on key intracellular pathways involved in the control of neuronal cell survival and apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Preparation and characterization of a set of monoclonal antibodies to TRAIL and TRAIL receptors DR 4 , DR 5 , DcR 1 , and DcR 2 . ^^^ Among TRAIL receptors , death receptor 4 ( DR 4 ) and DR 5 containing death domain ( DD ) in their cytoplasmic region mediate apoptosis signaling upon TRAIL binding , while decoy receptor 1 ( DcR 1 ) and DcR 2 with a truncated or non functional DD play `` decoy ' ' role . ^^^ In this study , we raised hybridomas secreting monoclonal antibodies against TRAIL ( FMU1 . 1 , 1 . 2 , 1 . 3 ) , DR 4 ( FMU1 . 4 ) , DR 5 ( FMU1 . 5 , 1 . 6 ) , DcR 1 ( FMU1 . 7 ) and DcR 2 ( FMU1 . 8 , 1 . 9 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
DR 4 expression was increased when Jurkat cells were treated with TRAIL , and DR 5 expression increased after exposing Molt 4 cells to TRAIL plus a low dose of doxorubicin for 24 h . ^^^ The expression of DR 4 and DR 5 in UCB mononuclear cells was unchanged after treatment with TRAIL , a low dose doxorubicin , or TRAIL plus a low dose of doxorubicin . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) and its receptor DR 5 were the early genes induced by the combination of cotylenin A and IFN alpha in lung carcinoma cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Four membrane bound receptors for TRAIL have been identified , two apoptosis mediating receptors , DR 4 and DR 5 , and two apoptosis inhibiting receptors , DcR 1 and DcR 2 . ^^^ In conclusion , marked changes were seen in the course of the adenoma carcinoma sequence with respect to the expression of TRAIL and TRAIL receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL R 2 ( DR 5 ) mediates apoptosis of synovial fibroblasts in rheumatoid arthritis . ^^^ Using two agonistic mAbs specific for TRAIL R 1 ( DR 4 ) and TRAIL R 2 ( DR 5 ) , we examined the expression and function of these death receptors in RA synovial fibroblast cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Death receptors DR 4 and DR 5 can induce and decoy receptors DcR 1 and DcR 2 can inhibit TRAIL mediated apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Analysis of TRAIL receptor expression using anti TRAIL death receptor 5 monoclonal antibodies . ^^^ Surface expression of the TRAIL receptor was determined by flow cytometric analysis measuring the binding of anti DR 5 mAb . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Of the two TRAIL receptors constitutively expressed by HL 60 ( TRAIL R 1 and TRAIL R 2 ) , only the former was involved in IkappaB degradation , as demonstrated by using agonistic anti TRAIL receptor antibodies . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The RT PCR and Western blotting results demonstrated that the levels of both mRNA and protein for death receptor 4 , death receptor 5 and decoy receptor 2 remained unchanged in response to etoposide , indicating that the synergistic effect of TRAIL and etoposide is not a result of increasing the expression for TRAIL receptors , but rather is associated with amplification of the mitochondrial signal pathway . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
PS 341 treatment by itself does not affect the levels of Bax , Bak , caspases 3 and 8 , c Flip or FADD , but elevates levels of TRAIL receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Four TRAIL / Apo2L receptors ( DR 4 , DR 5 , DcR 1 , and DcR 2 ) have been identified . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL induces apoptosis through its interaction with its two proapoptotic death receptors ( DRs ) , DR 4 and DR 5 . ^^^ We hypothesized that decreased expression of DRs DR 4 and DR 5 may contribute to TRAIL resistance . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In particular , RSV infection strongly up regulated the expression of tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) and its functional receptors death receptor 4 ( DR 4 ) and DR 5 . ^^^ These findings suggest that RSV infected cells in vivo are susceptible to killing through the TRAIL pathway by immune cells such as natural killer and CD 4 ( + ) cells that bear membrane bound TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
These cell lines expressed death receptors TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL R 2 , which were unaltered by treatment with CDDP , as assessed by flow cytometry . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In an in vitro binding assay , the intracellular domains of both TRAIL R 1 and TRAIL R 2 bound FADD : activation of PKC significantly inhibited this interaction suggesting that PKC may be targeting key apical components of death receptor signaling . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
To investigate the therapeutic potential of rhTRAIL , the expression of TRAIL and its apoptosis inducing receptors DR 4 and DR 5 was evaluated in tumors of stage 3 NSCLC patients . ^^^ DR 4 , DR 5 , and TRAIL expression were determined immunohistochemically in 87 tumors . ^^^ RESULTS : DR 4 , DR 5 , and TRAIL were expressed in 99 % , 82 % , and 91 % of the tumors , respectively . ^^^ Poorly differentiated areas showed strong staining intensity for DR 4 , DR 5 , and TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Ad5E1 tumor cells expressed DR 5 receptor for TRAIL and were susceptible to TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The surface expression of TRAIL R 1 was weakly detectable in the early intermediate phase of erythroid differentiation ( days 4 6 ; dim intermediate GPA expression ) , whereas a clear cut expression of TRAIL R 2 was observed through the entire course of erythroid differentiation ( up to days 12 14 ; bright GPA expression ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Surface expression of TRAIL receptors DR 4 and DR 5 was analysed by FACS . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL induces apoptosis in Adriamycin resistant MCF 7 cells already expressing high levels of death receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Furthermore , co methylation patterns were observed for the TRAIL receptor pairs DCR 1 and DCR 2 and between DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Of the two TRAIL death receptors ( DR 4 and DR 5 ) , melanoma cells primarily expressed DR 5 on cell surface . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
On the trail of a cereal killer : Exploring the biology of Magnaporthe grisea . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Human normal hepatocytes are susceptible to apoptosis signal mediated by both TRAIL R 1 and TRAIL R 2 . ^^^ We generated fully human monoclonal antibodies ( mAbs ) that bind specifically to TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL receptor 2 ( TRAIL R 2 ) , which mediate apoptosis signal when they ligate with TRAIL , to investigate the contribution of each receptor to induce tumor cell apoptosis and hepatocyte toxicity . ^^^ All of mAbs to TRAIL R 1 and TRAIL R 2 induced cell death in several cancer cell lines susceptible to TRAIL but not in human umbilical vein endothelial cells in vitro . ^^^ However , a subset of mAbs to TRAIL R 2 , which was characterized by the TRAIL blocking activity , did not show strong hepatocyte toxicity . ^^^ These results indicate that human normal hepatocytes are susceptible to both TRAIL R 1 and TRAIL R 2 mediated apoptosis signal . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Generally , sensitivity to FasL GFP correlated with cell surface FasR levels , but no such correlation was seen for TRAIL and its functional receptors , DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Normal peripheral blood derived monocyte differentiated macrophages expressed TRAIL R 2 ( P < 0 . 01 ) , but not TRAIL or the other TRAIL receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The TRAIL apoptotic signaling pathway has also been implicated in genotoxin induced apoptosis through upregulation of TRAIL death receptors DR 4 and DR 5 . ^^^ Preventing TRAIL from interacting with DR 4 and DR 5 decreases CLB induced apoptosis in CLL cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL receptor 2 ( DR 5 ) plays an important role in transducing apoptosis signals . ^^^ DR 5 was internalized into the cytoplasm where it recruited FAS associated death domain protein ( FADD ) under TRAIL stimulation in both sensitive and resistant cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL is expressed on different cells of the immune system and plays a role in both T cell and natural killer cell mediated tumor surveillance and suppression of suppressing tumor metastasis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Apoptosis pathways activated by death receptors of the tumour necrosis factor ( TNF ) family such as Fas , TNFR 1 , or the TRAIL receptors DR 4 and DR 5 are implicated in diverse diseases . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Although both TRAIL and its death receptor 5 were constitutively expressed in the liver , TRAIL expression by immune cells alone was sufficient to restore the sensitivity of TRAIL deficient mice to hepatitis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The 32 eyes were equally divided into four groups receiving graft without incubation with viral preparations , graft immersed in Dulbecco ' s minimum essential medium containing soluble human death receptor 5 ( sDR 5 ) before transplantation , graft carrying the recombinant adenovirus with TRAIL gene ( Ad TRAIL ) , and graft carrying the recombinant adenovirus with green fluorescent protein ( Ad GFP ) , respectively . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Finally , expression of the TRAIL receptors ( TRAILR ) 1 and TRAILR 2 in human cardiomyocytes was examined immunohistochemically . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Finally , thymocytes from mice exposed perinatally to TCDD showed higher levels of Fas , TRAIL , and DR 5 mRNA , but the levels of Bcl 2 , Bcl xL , and Bax were either unaltered or changed moderately . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Western blot analysis also shows that the low extracellular pH enhanced TRAIL cytotoxicity does not involve modulation of the levels of TRAIL receptors ( DR 4 , DR 5 , and DcR 2 ) , FLIP , inhibitor of apoptosis ( IAP ) , and Bcl 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Exposure of cells to TRAIL resulted in the upregulation of both death receptors DR 4 and DR 5 and apoptosis , as well as the activation of caspase 8 and 3 , increased phosphorylation of Jun N terminal kinase and p 38 kinase , and the reduction of bcl 2 and bcl xL proteins . ^^^ Preincubation with E 17 beta completely prevented both TRAIL induced DR 4 and DR 5 upregulation and apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Efforts to identify agents that up regulate DR 5 may be useful in cancer therapies restoring TRAIL sensitivity . . ^^^ Small interfering RNAs directed at proapoptotic p 53 targets reveal TRAIL receptor KILLER / DR5 contributes significantly to TRAIL sensitization , whereas Bak plays a minor role . ^^^ Our studies elucidate a mechanism for restoration of TRAIL sensitivity in MMR deficient Bax / human cancers through p 53 dependent activation of KILLER / DR5 and reconstitution of a type 1 death pathway . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL is a cytokine that can induce tumor specific apoptosis through its specific death receptors ( DR 4 and DR 5 ) and p 53 has been proven to increase the expression of death receptors . ^^^ Increased expressions of DR 4 and DR 5 of NCI H 157 and DR 4 of A 549 after p 53 overexpression were confirmed by flow cytometry . p 53 or TRAIL gene transfer increased sub G 1 fraction in cell cycle analysis and inhibited the tumor growth dose dependently and the degree was potentiated by co transfer . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL induced apoptosis through death receptor 5 ( DR 5 ) and was mediated by caspase 8 initiated extrinsic and intrinsic mitochondrial pathways in sensitive glioma cell lines . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Agonistic DR 4 and DR 5 antibodies against their TRAIL death receptor are being studied as another potential clinical option to induce apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL is known to bind to 4 different receptors , 2 proapoptotic ( DR 4 and DR 5 ) , and 2 potentially antiapoptotic receptors lacking death domains ( DcR 1 and DcR 2 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
However , to exploit fully its therapeutic potential , the characteristics of both the TRAIL receptor system and soluble TRAIL ( sTRAIL ) should be taken into account : first , the widespread expression of the various TRAIL receptors throughout the human body ; second , the differential binding affinities and crosslinking requirements of the agonistic receptors TRAIL R 1 and TRAIL R 2 ; and third , the solution behavior of particular sTRAIL preparations . ^^^ Target antigen binding converted soluble scFvC 54 : sTRAIL into a membrane bound form of TRAIL that was capable of signaling apoptosis not only through TRAIL R 1 but also through TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here we report that a monoclonal antibody ( mAb ) against the mouse TRAIL receptor , DR 5 , exhibited potent antitumor effects against TRAIL sensitive tumor cells in vivo by recruiting Fc receptor expressing innate immune cells , with no apparent systemic toxicity . ^^^ Notably , the anti DR 5 mAb mediated tumor rejection by innate immune cells efficiently evoked tumor specific T cell immunity that could also eradicate TRAIL resistant variants . ^^^ These results suggested that the antibody based therapy targeting DR 5 is an efficient strategy not only to eliminate TRAIL sensitive tumor cells , but also to induce tumor specific T cell memory that affords a long term protection from tumor recurrence . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RESULTS : Ad TRAIL infection induced expression of TRAIL in RCJ3 . 1C . 18 cells , increased expression of death receptor 4 ( DR 4 ) , and decreased expression of DR 5 and decoy receptor 1 ( DcR 1 ) . ^^^ Cartilage obtained from rats with experimentally induced OA showed increased expression of TRAIL and DR 4 and decreased expression of DR 5 and DcR 1 compared with control cartilage . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In the present study , expression of TRAIL and its apoptosis inducing death receptors ( DR 4 and DR 5 ) and inhibitory decoy receptor ( DcR 1 ) was studied in normal ovaries and in malignant ovarian tumors before and after chemotherapy to investigate the therapeutic potential of TRAIL . ^^^ METHODS : DR 4 , DR 5 , DcR 1 , and TRAIL were studied immunohistochemically in 5 normal ovaries , 15 stages I / II , and 26 stages III / IV primary ovarian cancers , including 19 paired tumor samples ( pre and post chemotherapy ) . ^^^ Of the ovarian cancers , 73 % expressed DR 4 , 51 % DR 5 , 46 % DcR 1 , and 34 % TRAIL . ^^^ Most primary and residual ovarian tumors expressed at least one TRAIL death receptor , while in residual tumors following chemotherapy , DR 5 was more frequently expressed . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Sodium butyrate sensitizes TRAIL mediated apoptosis by induction of transcription from the DR 5 gene promoter through Sp 1 sites in colon cancer cells . ^^^ In this study , we demonstrate for the first time that sodium butyrate selectively up regulated DR 5 but had no effect on the expression of the other TNF alpha related apoptosis inducing ligand ( TRAIL ) receptor , DR 4 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The combined cytotoxicity of TRAIL and EPI was significantly inhibited by the TRAIL neutralizing fusion protein DR 5 : Fc , although EPI did not affect the mRNA expression of DR 4 , DR 5 , DcR 1 or DcR 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
During TRAIL DR 4 , DR 5 signaling , this pathway is activated by interactions of activated Fas associated death domain with activated receptor interacting protein ( RIP ) , which in turn activates NF kappaB inducing kinase and phosphorylates IkappaB . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Irradiation augmented TRAIL induced apoptosis in breast cancer cells through up regulation of DR 5 , and subsequent activation of caspases 3 , 8 and 9 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RESULTS : TRAIL R 1 was constitutively expressed on cultured synovial fibroblasts from RA and OA , however , expression of TRAIL R 2 and TRAIL R 3 was not observed by immunohistochemistry and Western blot . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Enhancement of TRAIL induced apoptosis in MM cells by alpha TOS was also associated with upregulation of the TRAIL cognate death receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The structures of both TRAIL and the protein in complex with the extracellular domain of death receptor 5 ( sDR 5 ) were elucidated . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Recent studies show that death receptors ( DR 4 and DR 5 ) , decoy receptors ( DcR 1 and DcR 2 ) , and death inhibitors ( FLIP , FAP 1 , and IAP ) are responsible for the differential sensitivity to TRAIL of normal and tumor cells . ^^^ Several researchers have also shown that genotoxic agents , such as chemotherapeutic agents and ionizing radiation , enhance TRAIL induced cytotoxicity by increasing DR 5 gene expression or decreasing the intracellular level of FLIP , an antiapoptotic protein . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL has been shown to interact with the cell surface through five distinct receptors , named death receptor ( DR ) 4 , DR 5 , decoy receptor ( Dc ) R 1 , DcR 2 , and osteoprotegrin . ^^^ Tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) , first discovered in 1995 , was heralded as a selective killer of tumor cells , and its potential is still thought to be high . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
To date , only one apoptosis inducing TRAIL receptor ( murine KILLER [ MK ] ) has been identified in mice , and it is a homologue of human Death Receptor 5 . ^^^ TRAIL and KILLER are expressed and induce apoptosis in the murine preimplantation embryo . ^^^ TRAIL ( tumor necrosis factor [ TNF ] related apoptosis inducing ligand ) and KILLER are a death inducing ligand and receptor pair that belong to the TNF and TNF receptor superfamilies , respectively . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here we show that agonists of the TRAIL death receptor DR 5 potently induce apoptosis in human cells overexpressing the MYC oncogene , both in vitro and as tumor xenografts in vivo . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Moreover , exogenous DR 4 and KILLER / DR5 were not properly transported to the cell surface in the TRAIL resistant cells . ^^^ Interestingly , TRAIL resistant cells were resensitized to TRAIL by tunicamycin pretreatment , which increased cell surface expression of DR 4 and KILLER / DR5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we report that we deduced ligand binding domains based on the structure of apoptosis ligand receptor complex , and the synthetic peptide corresponding to residues 91 102 of DR 5 indeed showed specific binding to TRAIL molecule and inhibited TRAIL induced cell death both in L 929 cells and in HeLa cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
No correlation was found between the sensitivity of cells to TRAIL and the expression of TRAIL receptors DR 4 and DR 5 , and pro apoptotic proteins Bax and Bak . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In many mammalian cell types , engagement of the TRAIL / Apo2L death receptors DR 4 and DR 5 alters mitochondrial physiology , thereby promoting the release of pro apoptotic proteins normally contained within this organelle . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) signals apoptosis through two receptors , DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We show that both mRNA and protein of TRAIL receptors death receptors ( DR 4 , DR 5 ) and decoy receptors ( DcR 1 , DcR 2 ) are present in GCT stromal tumor cells . ^^^ Taken together , our findings suggest that TG is able to sensitize tumor cells of GCT to TRAIL induced cell death , perhaps in part through up regulating the death receptor DR 5 and down regulating the decoy receptor DcR 1 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We showed that the expression of death receptor DR 5 , but not DR 4 was up regulated and the decoy receptor DcR 1 was down regulated in the cells treated with 8 Cl Ado and the recombinant soluble TRAIL ( rsTRAIL , 95 281 a . a . ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The expression of tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) and TRAIL receptors was investigated in resting and cytokine activated purified primary human natural killer ( NK ) and CD 8 ( + ) T cells . ^^^ On activation , both cell types rapidly expressed TRAIL R 2 and TRAIL R 3 , whose expression peaked at day 10 of culture . ^^^ Notwithstanding the expression of TRAIL R 2 , recombinant TRAIL did not show any cytotoxic activity on either NK or CD 8 ( + ) T cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Results from colocalization and immunoprecipitation studies showed that IG 20 can interact with TRAIL death receptors ( DR ) , DR 4 and DR 5 and increase recruitment of FADD and caspase 8 into the TRAIL death inducing signaling complex ( DISC ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Osteoprotegerin ( OPG ) is a survival factor that exerts its effect by binding to tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) , thus preventing TRAIL from binding to the apoptosis receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Myc tagging along the TRAIL to death receptor 5 . ^^^ TRAIL mediates its effect via death receptors 4 ( DR 4 ) and DR 5 and appears to selectively induce apoptosis in cancer cells . ^^^ Recently , it has been reported that Myc oncoprotein by upregulating DR 5 appears to augment cellular susceptibility to TRAIL and to DR 5 agonistic antibodies . ^^^ Several previous studies have already established that various clinically relevant agents by upregulating DR 5 sensitize cells to TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
DR 5 as well as DR 4 were functional with regard to TRAIL mediated apoptosis induction in FLS ; however , DR 5 appeared be more efficient than DR 4 . ^^^ In addition to soluble DR 5 ( sDR 5 ) and sDR 4 , OPG administration significantly inhibited TRAIL induced apoptogenic activity . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RESULTS : Irradiation significantly augmented TRAIL induced apoptosis in prostate cancer cells through upregulation of DR 5 , Bax , and Bak , and induction of caspase activation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Membrane expression of TRAIL receptors DR 4 ( death receptor 4 ) , DR 5 ( pro apoptotic ) , DcR 1 ( decoy receptor 1 ) , DcR 2 ( anti apoptotic ) was assessed by flow cytometry . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Human and rat primary sub cultured vascular smooth muscle cells ( VSMCs ) showed clear expression of the death receptors TRAIL R 1 and TRAIL R 2 ; however , recombinant soluble TRAIL did not induce cell death when added to these cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The expression levels of DR 4 , DR 5 , DcR 1 and DcR 2 were measured in TRAIL treated and chemotherapeutic agent treated A 549 cells by Western blotting . ^^^ The expression levels of DR 4 and DR 5 were not significantly different and the expression of DcR 2 was slightly downregulated , but the expression of DcR 1 was not detected in non treated , TRAIL treated and chemotherapeutic agent treated A 549 cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Histone deacetylase inhibitors upregulate death receptor 5 / TRAIL R 2 and sensitize apoptosis induced by TRAIL / APO2 L in human malignant tumor cells . ^^^ Death receptor 5 ( DR 5 ) is a receptor for tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^ Death receptor 5 ( DR 5 ) is a receptor for tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^ Furthermore , TSA did not significantly induce DR 5 protein and HDACIs did not enhance TRAIL induced apoptosis in normal human peripheral blood mononuclear cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RT PCR and flow cytometric analyses demonstrated that TRAIL ' s effect is mediated primarily via the TRAIL R 2 receptor . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In addition to CD 95 , CD 40 activated CLL cells also express DR 5 , a receptor for tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) that is expressed by CD4+ CTL . ^^^ To evaluate whether ligation of CD 95 and / or DR 5 can induce apoptosis of CD 40 activated CLL cells , we generated artificial cytotoxic effector cells that express both human TRAIL and CD 178 ( Chinese hamster ovary [ CHO ] CD178 / TRAIL ) or only TRAIL ( CHO TRAIL ) or CD 178 ( CHO CD 178 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In particular , the expression of procaspase 8 gene and subsequent cleavage of caspase 8 were markedly reduced in HL 60 / FAK cells , while expression of TRAIL receptor 2 and 3 , TRADD , and FADD was equivalent in both types of cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The candidate tumor suppressor KILLER / DR5 is a DNA damage inducible p 53 regulated death receptor for the tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , a promising agent for cancer therapy . ^^^ The majority of studies on KILLER / DR5 have been focused on its role in TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL / FP induced no discernible changes in FLIP , DR 4 , DR 5 , Mcl 1 , or survivin expression , modest declines in levels of DcR 2 and c IAP , but resulted in the marked transcriptional downregulation of XIAP . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Chemotherapeutic drugs ( paclitaxel , vincristine , vinblastine , etoposide , doxorubicin , and camptothecin ) significantly augmented TRAIL induced apoptosis in cancer cells through up regulation of DR 4 , DR 5 , Bax , and Bak , and induction of caspase activation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Similarly , stable expression of a dominant negative TRAIL receptor DR 5 partially blocks IFN induced cell death . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here we show a novel mechanism by which FLICE like inhibitory protein ( c FLIP ) regulates apoptosis induced by tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) and one of its receptors , DR 5 . c FLIP is a critical regulator of the TNF family of cytokine receptor signaling . c FLIP has been postulated to prevent formation of the competent death inducing signaling complex ( DISC ) in a ligand dependent manner , through its interaction with FADD and / or caspase 8 . ^^^ In order to identify regulators of TRAIL function , we used the intracellular death domain ( DD ) of DR 5 as a target to screen a phage displayed combinatorial peptide library . ^^^ To the contrary , TRAIL treatment released c FLIP ( L ) from DR 5 , permitting the recruitment of FADD to the active DR 5 signaling complex . ^^^ Because TRAIL and DR 5 are ubiquitously expressed , the interaction of c FLIP ( L ) and DR 5 indicates a mechanism by which tumor selective apoptosis can be achieved through protecting normal cells from undergoing death receptor induced apoptosis . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
These glioblastoma cell lines expressed TRAIL R 2 , but not TRAIL R 1 , R 3 , or R 4 . ^^^ However , no correlation was observed between the TRAIL sensitivity and the TRAIL R 2 expression level , suggesting that there is an additional determinant of TRAIL sensitivity . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Adenovirus E 3 6 . 7K protein is required in conjunction with the E 3 RID protein complex for the internalization and degradation of TRAIL receptor 2 . ^^^ The experiments reported here show that TRAIL receptor 2 ( TR 2 ) is cleared from the cell surface in Ad infected cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Western blotting analyses revealed that IFN gamma dramatically increased the protein levels of interferon regulatory factor ( IRF ) 1 , but not TRAIL receptors ( DR 4 and DR 5 ) and pro apoptotic ( FADD and Bax ) and anti apoptotic factors ( Bcl 2 , Bcl XL , cIAP 1 , cIAP 2 and XIAP ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Although all antibodies used , recognized the respective human antigens , only the murine analogue of the human TRAIL R 2 epitope was also identified in the mouse brain . ^^^ In normal mice , TRAIL R 2 is not universally expressed throughout the brain but rather restricted to specific neuronal populations predominantly consisting of large neurons . ^^^ In weaver , the spatial patterns and relative densities of TRAIL R 2 labelling were virtually identical to those seen in wild types during the period of cell death in the cerebellum and the substantia nigra . ^^^ In Lurcher , TRAIL R 2 expression in cerebellar granule cells and inferior olivary neurons was identical to that in wildtypes but significantly reduced in Purkinje cells undergoing degeneration . ^^^ Thus , although TRAIL R 2 is found to be expressed in various cell types of the murine brain , cell death in weaver and Lurcher mutants is apparently not accompanied by an upregulation of TRAIL receptors . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In addition , some of the changes observed in SWB 77 were opposite to those seen in methionine dependent tumors , including expression of p 21 , TRAIL R 2 , and TIEG . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Moreover , silencing of DR 5 expression using small interfering RNA suppressed apoptosis induced by CDDO Me alone or by combination of CDDO Me and TRAIL , indicating that DR 5 up regulation is required for induction of apoptosis by CDDO Me and for enhancement of TRAIL induced apoptosis by CDDO Me . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We report in this study that mice deficient in TRAIL were partially resistant to primary listeriosis , and blocking TRAIL with a soluble death receptor 5 markedly ameliorated the disease . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) is a member of the TNF family of cytokines , which can induce apoptotic cell death in a variety of tumor cells by engaging the death receptors DR 4 and DR 5 , while sparing most normal cells . ^^^ Preclinical studies in mice and non human primates have shown the potential utility of recombinant soluble TRAIL and agonistic anti DR 5 or DR 4 antibodies for cancer therapy . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
To investigate the role of TRAIL mediated apoptosis , AGS cells were transduced with antisense constructs against the proapoptotic TRAIL receptors DR 4 and DR 5 . ^^^ Protein expression of Fas , TRAIL , DR 4 , and DR 5 was analyzed by Western blot . ^^^ In the presence of H . pylori , TRAIL ligand and DR 5 receptor were continuously expressed whereas DR 4 expression was increasing time dependently . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Western blot analysis showed that combined treatment with TRAIL and amiloride did not change the levels of TRAIL receptors ( death receptor ( DR ) 4 , DR 5 , and DcR 2 ( decoy recepter 2 ) or antiapoptotic proteins ( FLICE inhibitory protein ( FLIP ) , inhibitor of apoptosis ( IAP ) , and Bcl 2 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Frequent polymorphic changes but not mutations of TRAIL receptors DR 4 and DR 5 in mantle cell lymphoma and other B cell lymphoid neoplasms . ^^^ BACKGROUND AND OBJECTIVES : Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors DR 4 and DR 5 have been mapped to chromosome 8p21 22 , a region frequently deleted in different lymphoid neoplasms . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver . ^^^ Tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) is a key effector molecule expressed by natural killer ( NK ) cells and has been shown to prevent tumor initiation , growth , and metastasis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Our results demonstrated that 16 genes ; bad , bax , bcl 2 , bcl w , bcl 10 , caspase 3 , caspase 7 , caspase 8 , c myc , E 124 , GADD 45 , mdm 2 , NKkappab 1 , p 53 , p 21 , Rb and trail were up regulated and six genes ; caspase 1 , caspase 2 , DR 5 , E2F1 , FasL and iNOS did not changed in response to DES treatment in wild type mice compared to p53+ / knockout mice . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In conflict with the presence of active DR 4 and DR 5 receptors in both clones , U2OS cells exhibited only a low responsiveness to TRAIL , while the MDR U2OS subline did exhibit a marked TRAIL sensitivity . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the correlation between sensitivity to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) and expression level of death receptor 5 ( DR 5 ) on tumor cell surface . ^^^ Correlation between sensitivity to TRAIL and expression level of DR 5 on surface of tumor cells . ] . ^^^ The correlation between expression level of DR 5 and sensitivity to TRAIL was analyzed . ^^^ There was a significant positive correlation between the expression level of DR 5 with TRAIL inducing apoptosis ( r = 0 . 997 , P < 0 . 001 ) . ^^^ CONCLUSION : TRAIL inducing apoptosis is related to the expression level of DR 5 on surface of tumor cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Further results demonstrated that the expression of DR 5 and TRAIL was down regulated in the AdDeltaE1B55K co infected HLF cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Apoptosis in response to TRAIL was unrelated to DR 5 expression or endogenous p 53 status in a panel of 8 glioma cell lines . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Our data show that gliomas preferentially express TRAIL R 2 and that treatment with topotecan , a topoisomerase 1 inhibitor , significantly up regulates its expression as detected by flow cytometry and western blotting . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We first isolated human hepatocytes from patients and showed that the human hepatocytes expressed Fas but no TRAIL death receptor DR 4 and little DR 5 on the cell surface . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL is unusual as compared to the other cytokines of this family , as it interacts with a complex system of receptors consisting of two pro apoptotic death receptors ( TRAIL R 1 and TRAIL R 2 ) and three decoy receptors ( TRAIL R 3 , TRAIL R 4 and osteoprotegerin ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Expression levels of TRAIL death ( DR 4 and DR 5 ) and decoy ( DcR 1 and DcR 2 ) receptors were not different between primary and metastatic OC cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The facilitated DISC formation also occurred in the absence of TRAIL R 2 upregulation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here we report that : ( 1 ) HDACIs induce apoptosis of leukemic blasts , although oncogene expression is not sufficient to confer HDACI sensitivity to normal cells ; ( 2 ) apoptosis is p 53 independent and depends , both in vitro and in vivo , upon activation of the death receptor pathway ( TRAIL and Fas signaling pathways ) ; ( 3 ) TRAIL , DR 5 , FasL and Fas are upregulated by HDACIs in the leukemic cells , but not in normal hematopoietic progenitors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL signals through its receptors DR 4 and DR 5 , which can activate caspase 8 as well . ^^^ METHODS : The human Rb cell lines Y 79 and WERI Rb 1 were evaluated for their response to the Fas cross linking antibody CH 11 and recombinant TRAIL , as well as for cell surface presence and mutational status of Fas , DR 4 , and DR 5 by flow cytometry and genomic DNA sequencing , respectively . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Moreover , experiments performed with agonistic anti TRAIL receptor antibodies demonstrated that both TRAIL R 1 and TRAIL R 2 contributed , although at different levels , to TRAIL induced chemokine modulation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Upregulation of TRAIL receptor DR 5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RA FLSs were found to express constitutively TRAIL receptors 1 and 2 ( TRAIL R 1 and TRAIL R 2 ) on the cell surface . ^^^ TRAIL R 2 appears to be the main mediator of TRAIL induced stimulation , as RA FLS proliferation induced by an agonistic anti TRAIL R 2 antibody was comparable with that induced by TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The death ligands FasL and tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induce apoptosis by binding to their cognate cell surface death receptors Fas or death receptor ( DR ) 4 and DR 5 . ^^^ In normal cervix and CIN 1 samples , FasL , DR 4 , DR 5 , and TRAIL staining was mainly observed in the basal / parabasal layer , whereas Fas staining was localized in the superficial , more differentiated epithelial layer . ^^^ In contrast , homogeneous FasL , DR 4 , DR 5 , and TRAIL expression throughout the lesions was more frequently observed in CIN 3 and cervical cancer . ^^^ FasL , DR 4 , DR 5 , and TRAIL staining patterns were correlated , although TRAIL expression was more intense in low grade lesions . ^^^ CONCLUSION : The loss of Fas and the deregulation of FasL , DR 4 , DR 5 , and TRAIL in the CIN cervical cancer sequence suggest a possible functional role of these death ligands and receptors during cervical carcinogenesis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Moreover , the alteration of the S phase due to IFN beta promotes TRAIL dependent apoptosis by potentiating cell sensitivity to TRAIL , possibly through induction of a proapoptotic NF kappaB activity and TRAIL R 2 receptor expression . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The presence of BVR small interference RNA augmented the effect of As on levels of cytochrome c , TRAIL , and DR 5 mRNA and cleavage of poly ( ADP ribose ) polymerase . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Transformation by oncogenic RAS sensitizes human colon cells to TRAIL induced apoptosis by up regulating death receptor 4 and death receptor 5 through a MEK dependent pathway . ^^^ However , tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) is able to kill specific tumor cells through the engagement of its receptors , death receptor 4 ( DR 4 ) and death receptor 5 ( DR 5 ) , and the activation of apoptotic pathways , providing promising targets for anticancer therapies . ^^^ Our study reveals that transformation of the colon cell line Caco 2 by Ki and mainly by Ha ras oncogenes sensitizes these cells to TRAIL induced apoptosis by causing specific MEK dependent up regulation of DR 4 and DR 5 . ^^^ These observations taken together reveal that RAS MEK ERK1 / 2 signaling pathway can sensitize cells to TRAIL induced apoptosis by up regulating DR 4 and DR 5 and overall imply that TRAIL based therapeutic strategies using TRAIL agonists could be used in cases of human colon cancers bearing RAS mutations . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumour necrosis factor related apoptosis inducing ligand ( TRAIL ) receptor 2 ( TRAIL R 2 ) also known as TNFRSF10B ( tumour necrosis factor receptor ( TNFR ) super family 10b ) or KILLER / DR5 , a member of the TNFR family , is a promising candidate tumour suppressor gene at 8p21 22 . ^^^ We carried out mutation analysis of TRAIL R 2 in bladder cancer cell lines and in primary bladder tumours . ^^^ Our results suggest that if TRAIL R 2 is the target of LOH events in these cancers , inactivation of the remaining allele is by a mechanism other than mutation . . ^^^ Infrequent mutation of TRAIL receptor 2 ( TRAIL R2 / DR5 ) in transitional cell carcinoma of the bladder with 8p21 loss of heterozygosity . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) acts through the pro apoptotic DR 4 and DR 5 receptors in tumor cells without harming normal cells and will soon be tested in clinical trials as a novel anti cancer agent . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We showed that 5 Gy of 10 irradiation significantly up regulated the expression of death receptors Fas and DR 5 on the plasma membrane in gastric cancer cell lines MKN 45 and MKN 28 , lung cancer cell line A 549 , and prostate cancer cell line DU 145 , and that subsequent treatments with agonistic molecules for these death receptors , Fas antibody CH 11 and TRAIL , increased the formation of active fragment p 20 of caspase 3 followed by the induction of apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Absence of gene mutation in TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL receptor 2 ( TRAIL R 2 ) in chronic myelogenous leukemia and myelodysplastic syndrome , and analysis of mRNA Expressions of TRAIL and TRAIL related genes in chronic myelogenous leukemia . ^^^ We examined gene mutations in the death domains of TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL receptor 2 ( TRAIL R 2 ) , and in the TRAIL gene promoter in 46 chronic myelogenous leukemia ( CML ) patients . ^^^ In 23 of the 46 patients , all the coding regions of TRAIL R 2 were also examined . ^^^ Furthermore , no mutation in the death domains of TRAIL R 1 and TRAIL R 2 genes , which causes amino acid change , was found in 18 myelodysplastic syndrome ( MDS ) patients . ^^^ In addition , RPA revealed that the ratio of ( TRAIL R 1 plus TRAIL R 2 ) to TRAIL R 3 was also increased after IFN alpha stimulation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
IFN gamma pretreatment significantly suppressed the expression of death receptor 4 ( DR 4 ) and DR 5 on HUVECs , and inhibited apoptosis in response to TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
METHODS : Tissue specimens of 10 tooth germs , 40 benign ameloblastomas , and five malignant ameloblastomas were examined by reverse transcriptase polymerase chain reaction ( RT PCR ) and immunohistochemistry to determine the expression of TNFalpha , TNF receptor 1 ( TNFRI ) , TRAIL , TRAIL receptor 1 ( TRAIL R 1 ) , TRAIL R 2 , caspase 8 , and nuclear factor kappaB ( NF kappaB ) . ^^^ RESULTS : Expression of TNFalpha , TNFRI , TRAIL , TRAIL R 1 , TRAIL R 2 , and NF kappaB mRNA was detected in most samples of normal and neoplastic odontogenic tissues . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Interestingly , neutralization of TRAIL receptor 2 ( TRAIL R 2 ) , but not TRAIL R 1 , impaired apoptosis in a caspase 10 dependent manner , indicating that caspase 10 enhances TRAIL R 2 induced cell death . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Of four tumour necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors analysed , DR 4 was most commonly methylated ( 41 % ; compared with DcR 2 ( 26 % ) , DcR 1 ( 23 % ) and DR 5 ( 10 % ) ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In spite of the majority of B CLL lymphocytes expressed variable surface levels of `` death receptors ' ' TRAIL R 1 and TRAIL R 2 , the addition in culture of recombinant TRAIL increased ( > 20 % vs . controls ) the degree of spontaneous apoptosis in only 11 / 44 of the B CLL samples , had no effect in 19 / 44 , while it significantly increased leukemic cell survival in 14 / 44 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Functional expression of TRAIL and TRAIL R 2 during human megakaryocytic development . ^^^ The surface expression of both TRAIL and `` death receptor ' ' TRAIL R 2 became detectable starting from the early phase of megakaryocytic differentiation ( day 6 of culture ) and persisted at later ( days 10 14 ) culture times . ^^^ Conversely , addition in culture of TRAIL R 2 Fc chimera , which blocked the interaction between endogenous TRAIL and TRAIL R 2 on the surface of cultured megakaryocytic cells , increased the total megakaryocytic cell count . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In this study , we generated a novel agonist antibody to TRAIL receptor 2 ( TRAIL R 2 ) capable of inducing apoptosis without cross linking and elucidated its mode of action and efficacy . ^^^ EXPERIMENTAL DESIGN : A fully human antibody to TRAIL R 2 , KMTR 2 , was generated from KM Mouse immunized with TRAIL R 2 ectodomain . ^^^ Oligomerization of TRAIL R 2 was analyzed by size exclusion chromatography and confocal microscopy , and in vivo efficacy was examined in Colo 205 xenograft model . ^^^ RESULTS : KMTR 2 specifically recognized TRAIL R 2 and induced apoptosis with or without cross linking . ^^^ The antibody formed supracomplexes with soluble recombinant and membrane anchored TRAIL R 2 and enhanced clustering of TRAIL R 2 on cell surface without cross linking . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The selective tumoricidal activity of TRAIL is believed to be modulated by agonistic ( DR 4 and DR 5 ) and antagonistic receptors ( DcR 1 and DcR 2 ) , which appear to compete for ligand binding . ^^^ The DR 5 transcripts from one TRAIL sensitive , one partially TRAIL resistant , and one TRAIL resistant cell line were subsequently sequenced . ^^^ The DR 5 sequences in T98G , A 172 , and U373MG cell lines were identical to published sequences despite these differences in sensitivity to TRAIL . ^^^ The overexpression of DR 5 induced apoptotic cell death in glioma cells without TRAIL and was able to overcome the resistance to TRAIL demonstrated in U 373 cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumour necrosis factor related apoptosis inducing ligand ( TRAIL ) induces apoptosis in a variety of tumour cells through activation of TRAIL R 1 and TRAIL R 2 death signalling receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
OBJECTIVE : To determine the potential immediate applicability of tumor necrosis factor related apoptosis inducing ligand receptor 1 ( TRAIL R 1 ) and TRAIL R 2 , the apoptotic forms of TRAIL Rs , for preclinical testing . ^^^ DESIGN AND SETTING : Head and neck squamous cell carcinoma ( HNSCC ) tumors were studied for TRAIL R 1 and TRAIL R 2 expression by immunohistochemical analysis . ^^^ MAIN OUTCOME MEASURES : The expression of TRAIL R 1 and TRAIL R 2 and the presence of the TRAIL R 1 polymorphisms C626G and G422A . ^^^ RESULTS : Fewer than 25 % of HNSCC tumor cells expressed TRAIL R 1 and TRAIL R 2 . ^^^ Surrounding tumor infiltrating polymorphonuclear cells expressed TRAIL R 1 and TRAIL R 2 in 12 ( 32 % ) and 14 ( 38 % ) of cases , respectively . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL receptor 1 ( DR 4 ) and TRAIL receptor 2 ( DR 5 ) were upregulated under the treatment of doxorubicin and verified to be responsible for TRAIL mediated signal transduction . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Interestingly , the pro apoptotic activity of the drug is not due to the relief of oncogene mediated inhibition of the p 53 tumor suppressor pathway but , instead , relies on the selective upregulation of the death receptors DR 5 and Fas and their cognate ligands TRAIL and FasL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumour necrosis factor related apoptosis inducing ligand ( TRAIL ) and antibodies against TRAIL receptors death receptor 4 ( DR 4 ) and death receptor 5 ( DR 5 ) are under investigation for cancer therapy . ^^^ BAX mutations were found in 6 / 42 MSI H cancers with similar apoptotic indices and expression of DR 4 , DR 5 and TRAIL in BAX mutant and wild type cases . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL R 1 is distinctively expressed on B lymphocytes , TRAIL R 2 on monocytes , TRAIL R 3 on neutrophils and most impressively , CD8+ lymphocytes and NKT lymphocytes but not CD4+ lymphocytes express TRAIL R4 . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
DR 5 , which is a mouse TRAIL receptor , was also induced to express after virus infection . ^^^ Expression of both TRAIL and DR 5 mRNAs was reduced to normal level at 6 weeks after virus infection . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
From a mechanistic standpoint , we show that CDDO and CDDO Im down regulate the antiapoptotic protein c FLIP ( L ) , and up regulate cell surface TRAIL receptors DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Contrary to literature reports that TRAIL induced apoptosis occurs primarily via signaling through TRAIL R 2 , CLL cells , in the presence of HDACi , undergo predominantly TRAIL R 1 mediated apoptosis . ^^^ Consequently , Apo2L / TRAIL , which signals primarily through TRAIL R 2 , is virtually devoid of activity against CLL cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Our previous studies have shown that luteolin , a naturally occurring flavonoid , induces the up regulation of death receptor 5 ( DR 5 ) , which is a receptor for TRAIL . ^^^ Also , human recombinant DR5 / Fc chimera protein , caspase inhibitors , and DR 5 siRNA efficiently reduced apoptosis induced by co treatment with luteolin and TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Death receptor 5 ( DR 5 , TRAIL R 2 ) is a proapoptotic protein considered to be a potential target for cancer therapy , and its expression is mediated by NF kappaB . ^^^ Death receptor 5 ( DR 5 , TRAIL R 2 ) is a proapoptotic protein considered to be a potential target for cancer therapy , and its expression is mediated by NF kappaB . ^^^ Blockage of DR 5 activation decreased HDAC inhibitor induced apoptosis , and a combination of HDAC inhibitors and TRAIL increased apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Curcumin sensitizes tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induced apoptosis through reactive oxygen species mediated upregulation of death receptor 5 ( DR 5 ) . ^^^ Not only the pretreatment with N acetylcystine but also the ectopic expression of peroxiredoxin 2 , an antioxidative protein , dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination , blocking the curcumin mediated DR 5 upregulation . ^^^ Taken together , the present study demonstrates that curcumin enhances TRAIL induced apoptosis by ROS mediated DR 5 upregulation . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The mRNA for TRAIL and its receptor , DR 5 , are induced following viral infection . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Proteasome inhibitors induce the expression of death receptor 5 ( DR 5 ) , a receptor for TRAIL , and sensitize cancer cells to TRAIL induced apoptosis ; however , the molecular mechanism of DR 5 up regulation has not been elucidated . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The expression of TRAIL receptors ( DR 4 , DR 5 , DcR 1 , and DcR 2 ) and the expression of death signal transducing proteins were investigated . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Extensive regions of the FADD death domain are required for binding to the TRAIL receptor DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In BT 474 cells , but not SKBr 3 cells , inhibition of the HER2 / phosphatidylinositol 3 ' kinase ( PI3K ) / Akt pathway resulted in downregulation of the pro apoptotic receptors TRAIL receptor 1 ( TRAIL R 1 ) and TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Death receptor 5 ( DR5 / TRAIL R 2 ) is an apoptosis inducing membrane receptor for tumor necrosis factor related apoptosis inducing ligand ( TRAIL / Apo2L ) . ^^^ In this study , we showed that tunicamycin , a naturally occurring antibiotic , is a potent enhancer of TRAIL induced apoptosis through up regulation of DR 5 expression . ^^^ Furthermore , the tunicamycin mediated sensitization to TRAIL was efficiently reduced by DR 5 small interfering RNA , suggesting that the sensitization was mediated through induction of DR 5 expression . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Low doses of SAHA or TSA enhanced the cytotoxic and apoptotic effects of TRAIL and upregulated the surface expression of TRAIL death receptors ( DR 4 and / or DR 5 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The role of the DR 5 mediated extrinsic apoptotic pathway was further studied in the three human glioma cell lines ; 50 ng / ml of the DR 5 ligand TRAIL ( tumor necrosis factor related apoptosis inducing ligand ) and 2 microM 2 ME showed no synergism , as determined by MTT assays . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Evaluating the expression and prognostic value of TRAIL R 1 and TRAIL R 2 in breast cancer . ^^^ PURPOSE : The cell surface receptors tumor necrosis factor related apoptosis inducing ligand receptor 1 ( TRAIL R 1 ) and TRAIL R 2 transmit apoptotic signals , and agents that activate these receptors are in clinical development . ^^^ We sought to determine the expression and prognostic value of TRAIL R 1 and TRAIL R 2 in early stage breast cancer . ^^^ TRAIL R 1 and TRAIL R 2 expression were similarly studied on 95 unmatched normal breast specimens . ^^^ High TRAIL R 2 expression strongly correlated with decreased survival ( P = 0 . 0005 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induces apoptosis via the death receptors DR 4 and DR 5 in transformed cells in vitro and exhibits potent antitumor activity in vivo with minor side effects . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
CONCLUSION : The data suggested that the enhanced infiltration of FasL and / or TRAIL expressing leukocytes ( CD4+ T cells , CD8+ T cells , natural killer cells and macrophages ) and the induction of Fas expression on tumor cells may play an important role in the therapeutic effect of BCG instillation . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The present study investigates the expression of TRAIL death receptor 5 ( DR 5 ) in the peripheral blood mononuclear cells ( PBMCs ) of HIV 1 infected patients and its role in CD 4 ( + ) T cell death . ^^^ CD 4 ( + ) , but not CD 8 ( + ) , T cells from uninfected donors expressed TRAIL , DR 5 , and activated caspase 3 when cultured with infectious or noninfectious HIV 1 , resulting in preferential apoptosis of CD 4 ( + ) T cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
BACKGROUND : In this work we studied the relationship between the enhanced expression of DR 5 receptor and the effect of combination of TRAIL and ionizing radiation on cell cycle arrest and apoptosis induction in human leukemia cell line HL 60 . ^^^ An increase of DR 5 receptor positivity after a dose of 2 Gy was not statistically significant and application of TRAIL 48 h after irradiation did not increase the apoptosis induction . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The down regulated genes were TRAIL , TNFR , AP 13 , IGFBP 3 , SARP 3 , PKB , IGFBP , CASP 7 , CASP 9 , TNFSF 6 , TRICK2A , CAS , TRAIL R 2 , RATS 1 , hTRIP , TNFb and TNFRSF 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In the present study , expressions of TRAIL receptors , death receptor 4 ( DR 4 ) and DR 5 , were detected in all ameloblastoma tissues by immunohistochemistry as well as in AM 1 cells by immunofluorescence . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Characterization of 8p21 . 3 chromosomal deletions in B cell lymphoma : TRAIL R 1 and TRAIL R 2 as candidate dosage dependent tumor suppressor genes . ^^^ Gene expression analysis and quantitative reverse transcriptase polymerase chain reaction ( QRT PCR ) showed down regulation of TRAIL R 1 and TRAIL R 2 receptor genes as a consistent event in B NHL with 8p21 . 3 loss . ^^^ Resistance to apoptosis of cell lines with 8p21 . 3 deletion was reversed by restoration of TRAIL R 1 or TRAIL R 2 expression by gene transfection . ^^^ Our data suggest that TRAIL R 1 and TRAIL R 2 act as dosage dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL induced apoptosis in B cell lymphoma . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Western blot analysis showed that combined treatment with TRAIL and amiloride did not change the levels of TRAIL receptors ( DR 4 , DR 5 , and DcR 2 ) and anti apoptotic proteins ( FLIP , IAP , and Bcl 2 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
A monoclonal antibody , TRA 8 , specifically binds to death receptor 5 , one of two death receptors bound by tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL R 1 and TRAIL R 2 in primary and cultured lymphoma cells : induction of apoptosis and enhancement of doxorubicin and bortezomib induced cell death . ^^^ TRAIL has four exclusive receptors , two of which ( TRAIL R 1 , TRAIL R 2 ) are death receptors . ^^^ Using two fully human selective agonistic monoclonal antibodies to the TRAIL death receptors TRAIL R 1 ( HGS ETR 1 ) and TRAIL R 2 ( HGS ETR 2 ) this study demonstrated that both monoclonal antibodies activated caspase 8 and induced cell death in five of nine human lymphoma cell lines , and induced > 10 % cell death in 67 % and 70 % , respectively , of 27 primary lymphoma cells , and > 20 % cell death in at least one thirds of the samples . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Treatment induced cytosolic accumulation of p 53 and enhanced the susceptibility of RASFs to apoptosis mediated by TRAIL R 2 ( DR 5 ) but not Fas . ^^^ A specific role for p 53 in TRAIL R 2 mediated apoptosis was indicated by the ability of p 53 siRNA to significantly reduce RASF apoptosis and by the reduced apoptosis of RASFs bearing p 53 mutations on treatment with anti DR 5 antibody or anti DR 5 antibody plus lactacystin . p 53 immunoprecipitation followed by mass spectrometry identified a vimentin p 53 complex , an interaction that was confirmed by reciprocal vimentin p 53 immunoprecipitation and by co immunofluorescence . ^^^ Interestingly , human caspase 4 cleaved human vimentin , and blockade of caspase 4 with a chemical inhibitor or with specific siRNA significantly inhibited TRAIL R 2 mediated apoptosis of RASFs . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Immunohistochemistry was performed for cell cycle regulators [ p 53 , p 21 , p 27 , p 16 , cyclin D 1 , Rb ] , apoptosis related proteins [ Fas , Fas L , FADD , TRAIL , DR 4 , DR 5 , caspase 8 , caspase 3 , bcl 2 , Bax ] , tumor suppressor proteins [ beta catenin , E cadherin , FHIT , Smad 4 , VHL , PTEN , KAI 1 ] , and oncoproteins [ c myc , COX 2 , EGFR ] . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Five distinct receptors have been described for TRAIL : TRAIL R 1 ( DR 4 ) , TRAIL R 2 ( DR 5 , TRICK ) , TRAIL R 3 ( TRID , DcR 1 ) , TRAIL R 4 ( TRUNDD , DcR 2 ) , and osteoprotegerin . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Here , we have generated and characterised a set of monoclonal antibodies , together with mAbs from the HLDA workshop , against DcR 1 , DcR 2 , DR 4 , DR 5 , TRAIL , APRIL , BAFF , BAFF R , BCMA , and TACI , which may be useful in phenotypic and functional studies of the role of TNF and TNF receptor family in immune function and regulation in relation to health and disease . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Previously , we showed that although most adult T cell leukemia / lymphoma ( ATLL ) cells express the TRAIL death receptor DR 4 ( TRAIL R 1 ) or DR 5 ( TRAIL R 2 ) , they are resistant to TRAIL . ^^^ BB 1 increased the level of TRAIL R 2 promoter activity and surface protein expression in a p 53 independent manner . ^^^ TRAIL R 2 siRNA inhibited the synergism , indicating that sensitization was caused by the increase of TRAIL R 2 expression . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Distinct function of monoclonal antibody to TRAIL R 2 as potentiator or inhibitor of the ligand TRAIL induced apoptosis . ^^^ Although hepatocytes are susceptible to apoptotic signals mediated by TRAIL receptor 2 ( TRAIL R 2 ) , we previously reported that some anti TRAIL R 2 monoclonal antibodies ( mAbs ) produce little hepatocyte toxicity . ^^^ The hepatocyte toxic mAbs did not compete with TRAIL for binding to TRAIL R 2 , and potentiated ligand activity in both cancer cells and hepatocytes . ^^^ A neutralizing antibody to TRAIL inhibited hepatocyte death by anti TRAIL R 2 mAbs , suggesting that the toxicity may reflect their ability to potentiate membrane bound TRAIL on hepatocytes . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to TRAIL / Apo 2L induced apoptosis by enhancing TRAIL R 2 expression . ^^^ Both sodium butyrate and trichostatin A treatment also increased mRNA and surface expression of TRAIL receptor 2 that was dependent on the transcription factor Sp 1 , thus providing a possible mechanism behind the increased sensitivity to TRAIL / Apo 2L . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The cytokine TRAIL ( tumor necrosis factor alpha related apoptosis inducing ligand ) as well as agonistic antibodies that bind to the TRAIL receptors , death receptor 4 ( DR 4 ) and DR 5 , are undergoing preclinical and early clinical evaluation as potential therapeutic agents for a variety of hematological and nonhematological malignancies . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Flow cytometry analysis revealed that both TRAIL R 2 and TRAIL were up regulated on the cell surface of HepG 2 cells with AdCMVLacZ infection . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Some members of the DR family , CD 95 and the TRAIL receptors DR 4 and DR 5 , directly bind FADD , whereas others , such as TNF receptor 1 and DR 3 , initially bind another adaptor protein , TRADD , which then recruits FADD . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Given that sulindac sulfide activated caspase 8 and increased membrane death receptor ( DR 4 and DR 5 ) protein levels , we evaluated its combination with the endogenous death receptor ligand tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Its expression , like the other three TRAIL receptors ( i . e . , DR 4 , DR 5 , and DcR 1 ) , is regulated by p 53 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
AD 5 10 does not compete with TRAIL for binding to DR 5 and synergizes with TRAIL to induce apoptosis of tumor cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In spite of the presence of TRAIL R 1 and TRAIL R 2 `` death receptors , ' ' recombinant TRAIL was not cytotoxic for tsFHI cells . ^^^ The differentiation inducing activity of TRAIL was abolished by pre incubation with a Fc TRAIL R 2 chimera . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors , including TNFRSF10A and TNFRSF10B , are located within this chromosomal region . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
No changes were observed in DR 4 , DR 5 , DcR 1 , and TRAIL mRNA and protein levels in prostate after castration . ( 2 ) A specific decrease in DcR 2 expression was observed in the ventral prostate after treatment of rats with the anti androgen flutamide . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Interestingly , these effects were not dependent on activation of DR 5 by its ligand TRAIL . ^^^ These results indicate that c FLIP inhibits TRAIL independent , DR 5 and caspase 8 dependent apoptosis in response to chemotherapy in CRC cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
OBJECTIVES : There is substantial evidence that tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) causes apoptosis via activation of death receptors 4 and 5 ( DR 4 and DR 5 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Two of them , death receptors 4 and 5 ( DR 4 and DR 5 ) , induce apoptosis , whereas decoy receptors 1 and 2 ( DcR 1 and DcR 2 ) are unable to evoke cell death upon TRAIL binding . ^^^ We observed frequent expression of TRAIL DcR 1 and DcR 2 , while expression of DR 4 and DR 5 was less frequent . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
HDAC inhibitors enhance the apoptosis inducing potential of TRAIL in leukemia cells ( HL 60 , Jurkat , K 562 , and U 937 ) through multiple mechanisms ; up regulation of DR 4 , DR 5 , Bak , Bax , Bim , Noxa and PUMA , down regulation of IAPs , Mcl 1 , Bcl 2 , Bcl XL and cFLIP , release of mitochondrial proteins ( cytochrome c , Smac / DIABLO and Omi / Htr2 ) to the cytosol , induction of p21WAF1 / CIP1 and p27KIP1 , activation of caspase 3 and cleavage of poly ( ADP ribose ) polymerase ( PARP ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Expression of the TRAIL receptor 2 ( DR 5 ) on the cell surface of RASF was analysed by flow cytometry . ^^^ RASF express DR 5 ( TRAIL receptor 2 ) , but treatment of the cells with TSA for 24 hours did not change the expression level of DR 5 , as it is shown for cancer cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
MG 132 massively induced TRAIL receptor DR 4 and DR 5 membrane expression in HeLa , whereas in SiHa only DR 5 membrane expression was upregulated from almost undetectable to high levels . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Subsequently , we investigated the detailed apoptotic pathway of ACA and further demonstrated that ACA up regulates the expression of both TNF related apoptosis inducing ligand / Apo2 ligand ( TRAIL / Apo2L ) and TRAIL receptor death receptor 5 ( DR 5 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The `` decoy receptors ' ' TRAIL R 3 ( TR 3 ) and TRAIL R 4 ( TR 4 ) were believed to negatively regulate TRAIL induced cytotoxicity by competing for ligand binding with TRAIL R 1 ( TR 1 ) and TRAIL R 2 ( TR 2 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
U2OS human osteosarcoma cells express TRAIL R 2 but are resistant to TRAIL induced apoptosis . however , the genotoxic drugs , Doxorubicin and Cisplatin , are able to sensitize U2OS cells to TRAIL , without affecting their surface expression of either death or decoy TRAIL receptors . ^^^ TRAIL R 2 downmodulation by siRNAs completely abolished the TRAIL induced apoptosis of genotoxin treated U2OS cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) and its agonistic antibodies , which are currently in early clinical trials for treating various malignancies , induce apoptosis through triggering of either TRAIL R 1 or TRAIL R 2 . ^^^ We have now synthesized mutant forms of TRAIL specific for TRAIL R 1 or TRAIL R 2 . ^^^ Thus , no significant therapeutic benefit can be anticipated from treating such patients with agents currently in clinical trials that signal predominantly through TRAIL R 2 , such as HGS ETR 2 or Apo2L / TRAIL . ^^^ Our study highlights the necessity to determine whether primary cells from a particular tumor signal via TRAIL R 1 or TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Cyclooxygenase 2 inhibition sensitizes human colon carcinoma cells to TRAIL induced apoptosis through clustering of DR 5 and concentrating death inducing signaling complex components into ceramide enriched caveolae . ^^^ We have shown that COX 2 inhibition sensitizes human colon carcinoma cells to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induced apoptosis by inducing clustering of the TRAIL receptor DR 5 at the cell surface and the redistribution of the death inducing signaling complex components ( DR 5 , FADD , and procaspase 8 ) into cholesterol rich and ceramide rich domains known as caveolae . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR 5 upregulation and caspase 8 dependent pathway . ^^^ Thus , our results suggest that adenovirus E1A sensitizes P HLF cells to TRAIL induced apoptosis involving DR 5 upregulation and the caspase 8 dependent pathway . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : We used an arrayed panel of epithelial ovarian cancer tissue to assess the protein expression of TRAIL and the clinically most relevant members of its pathway death receptors 4 and 5 ( DR 4 and DR 5 ) and the long form of FLICE inhibitory protein ( FLIPL ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We show that after contact with the influenza virus , GEN2 . 2 , as well as normal PDC , acquires TRAIL and killer activity against TRAIL sensitive target cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Although chemotherapy treatment did not modulate mRNA or cell surface expression of the TRAIL receptors death receptor 4 , death receptor 5 , decoy receptor 1 , or decoy receptor 2 , it was found to down regulate expression of the caspase 8 inhibitor , c FLIP . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
HDAC inhibition , especially with sodium butyrate and trichostatin A , led to increased TRAIL R 2 gene transcription that correlated with increased TRAIL R 2 surface expression . ^^^ The increased TRAIL R 2 levels also resulted in accelerated death inducing signaling complex ( DISC ) formation , caspase activation , and loss of mitochondrial membrane potential , which all contributed to the increase in tumor cell death . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In cancer patients , phase 1 and 2 clinical trials using agonistic mAbs that engage the human TRAIL receptors DR 4 and DR 5 have also provided encouraging results . ^^^ It is now evident that TRAIL suppresses autoimmune disease in various experimental animal models , suggesting that the therapeutic value of recombinant TRAIL and agonistic DR 4 and DR 5 mAbs might also extend to the suppression of autoimmune disease . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Pre treatment with the TRAIL antagonistic protein TRAIL R 2 : Fc prevented the death of T lymphocytes caused by activated human astroglioma cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In PLB 985 , but not WY 1 cells , RA induced TRAIL and its DR 4 and DR 5 receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Sulforaphane sensitizes tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) resistant hepatoma cells to TRAIL induced apoptosis through reactive oxygen species mediated up regulation of DR 5 . ^^^ We found that sulforaphane treatment significantly up regulated mRNA and protein levels of DR 5 , a death receptor of TRAIL . ^^^ Furthermore , the sulforaphane mediated sensitization to TRAIL was efficiently reduced by administration of a blocking antibody or small interfering RNAs for DR 5 . ^^^ These results collectively indicate that sulforaphane induced generation of ROS and the subsequent up regulation of DR 5 are critical for triggering and amplifying TRAIL induced apoptotic signaling . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
It also induced TRAIL R 2 expression , accelerated the death inducing signaling complex formation and enhanced caspase 8 activation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Functional expression of TRAIL receptors TRAIL R 1 and TRAIL R 2 in esophageal adenocarcinoma . ^^^ TRAIL induces apoptosis by interacting with its receptors TRAIL R 1 and TRAIL R 2 . ^^^ Recently , new humanized agonistic anti TRAIL R 1 and anti TRAIL R 2 antibodies have been developed , and are undergoing phase I / II clinical trails . ^^^ The aim of this study was to determine whether human EA tissue express TRAIL R 1 and / or TRAIL R 2 , and whether EA cell lines Bic 1 and Seg 1 expresses functional TRAIL R 1 and / or TRAIL R 2 . ^^^ The expression of TRAIL R 1 and TRAIL R 2 was determined in sections from 18 human EA by immunohistochemistry ( IHC ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Inhibition of the phosphatidylinositol 3 kinase ( PI3K ) was equally efficient in sensitising leukaemic cells to TRAIL with similar effects on DR 5 and FLIPS expression , suggesting that ATO may in part act through inhibition of the PI3K / Akt signalling pathway . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TSA induced the transcription of TRAIL death receptor DR 5 without affecting the transcription of DR 4 and the decoy receptors ; DcR 1 and DcR 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In contrast , proteasome inhibition induced alterations in TRAIL , death receptor 5 , and Bim could not be implicated in the apoptotic response . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
We report here that death receptor 5 ( DR 5 ) , tumor necrosis factor receptor 1 ( TNF R 1 ) , and Fas receptor ( FasR ) are all located in the caveolin 1 enriched membrane fractions , and TRAIL caused the translocation of DR 5 , FasR , and TNF R 1 to the caveolar fractions . ^^^ Using confocal microscopy , we found that DR 5 , caspase 8 , and caveolin 1 became progressively concentrated in blebs of plasmalemma as they formed in response to TRAIL . ^^^ Our results provide the first evidence for the caveolar localization of TNF R 1 and DR 5 and the coordinated redistribution among membrane fractions of several death receptors in response to TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The interferon ( IFN ) gamma induced TRAIL effector mechanism is a vital component of cancer immunosurveillance by natural killer ( NK ) cells in mice . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
H5N1 / 97 infected MDMs exhibited the strongest induction of apoptosis in Jurkat T cells , and it could be reduced by TRAIL receptor 2 blocking antibody . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Histochemical studies and immunohistochemical analysis for the localisation of TRAIL , DR 5 and MMP 13 were also performed . ^^^ MMP 13 was overexpressed , mainly in fibroblasts and epithelial cells , while positivity for TRAIL and DR 5 was detected on alveolar surfaces and in the vascular stroma . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Alpha tocopheryl succinate induces DR 4 and DR 5 expression by a p 53 dependent route : implication for sensitisation of resistant cancer cells to TRAIL apoptosis . ^^^ MM cells selected for TRAIL resistance expressed low cell surface levels of DR 4 and DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Additional in vitro studies revealed that the apoptosis of erythroblasts and the expression of FasL , TRAIL , TRAIL R 1 and TRAIL R 2 was lower in cultures with thalidomide than in control cultures . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
The aim of this study was to quantify the expression of the death regulating receptors TRAIL R 1 , TRAIL R 2 and TRAIL on primary GBM specimens and to correlate this expression with survival . ^^^ TRAIL R 2 expression was significantly higher expressed than TRAIL R 1 ( P=0 . 005 ) . ^^^ The antigenic load of TRAIL R 2 was positively correlated with survival ( P=0 . 02 ) . ^^^ Multivariate analysis of TRAIL R 2 staining intensity and antigenic load , within the study group ( P=0 . 004 , respectively , P=0 . 03 ) and the subgroup ( P=0 . 002 , respectively , P=0 . 004 ) , showed a significant association with survival . ^^^ CONCLUSIONS : TRAIL R 1 and TRAIL R 2 expression on tumor cells are independent prognostic factors for survival in patients with a glioblastoma multiforme . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TRAIL death receptors ( DR 4 , DR 5 ) are weakly expressed at mRNA , protein , and cell surface levels and thus fail to mediate the assembly of the DISC in human astrocytes . ^^^ Overexpression of DR 5 restores TRAIL signaling pathways and sensitizes the human astrocytes to TRAIL induced apoptosis if CaMKII kinase activity or expression of PEA 15 and c FLIP is inhibited ; the results suggest that CaMKII mediated pathways prevent TRAIL induced apoptosis in human astrocytes under conditions in which TRAIL death receptors are upregulated . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
SFN upregulated the expression of death receptor 5 ( DR 5 ) , a receptor for TRAIL , at mRNA and protein levels in a dose dependent manner . ^^^ Sulforaphane enhances TRAIL induced apoptosis through the induction of DR 5 expression in human osteosarcoma cells . ^^^ In addition , the SFN mediated sensitization to TRAIL was reduced by DR 5 siRNA , suggesting that the sensitization was at least partially mediated through the induction of DR 5 expression . ^^^ On the other hand , SFN neither induced DR 5 protein expression or enhanced TRAIL induced apoptosis in normal human peripheral blood mononuclear cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
No heat mediated alteration in the antibody recognition of cell surface DR 4 and DR 5 TRAIL receptors was observed . ^^^ However , in the presence of TRAIL , a long lasting attenuation in the antibody detection of DR 4 and DR 5 was observed in heat shock treated cells that correlated with the enhanced apoptogenic efficiency of TRAIL . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
This chapter focuses on the relevance of CD95L / FasL and TRAIL for the tumour surveillance function of natural killer cells and cytotoxic T cells and discuss current concepts of utilizing these ligands in tumour therapy . . ^^^ The membrane bound death ligands CD95L / FasL and TRAIL , which activate the corresponding death receptors CD95 / Fas , TRAILR 1 and TRAILR 2 , induce apoptosis in many tumour cells , but can also elicit an inflammatory response . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Curcumin sensitizes tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) mediated apoptosis through CHOP independent DR 5 upregulation . ^^^ Death receptor DR 5 ( DR5 / TRAIL R 2 ) is an apoptosis inducing membrane receptor for tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^ In this study , we showed that curcumin , a plant product containing the phenolic phytochemical , is a potent enhancer of TRAIL induced apoptosis through upregulation of DR 5 expression . ^^^ Both treatment with DR5 / Fc chimeric protein and silencing of DR 5 expression using small interfering RNA ( siRNA ) attenuated curcumin plus TRAIL induced apoptosis , showing that the critical role of DR 5 in this cell death . ^^^ However , suppression of CHOP expression by small interfering RNA did not abrogate the curcumin mediated induction of DR 5 and the cell death induced by curcumin plus TRAIL , demonstrating that CHOP is not involved in curcumin induced DR 5 upregulation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Apoptosis induction by TRAIL in these cells could only be fully inhibited by concomitant blockade of TRAIL receptor 1 and TRAIL receptor 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Chemotherapy agents induced upregulation of cell surface TRAIL R 2 ( DR 5 ) and Fas ( CD 95 ) expression , increasing the capacity for NKT cells to recognize and kill via TRAIL and FasL mediated pathways . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In this report , we show for the first time that apigenin markedly induces the expression of death receptor 5 ( DR 5 ) and synergistically acts with exogenous soluble recombinant human tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) to induce apoptosis in malignant tumor cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
RESULTS : CGH detected loss of the chromosomal regions that contain the following genes : 8p12 p 23 ( DR 4 and DR 5 ) , 2q33 34 ( caspase 8 ) , 11q13 . 3 ( FADD ) , 22q11 . 2 ( Bid ) , and 12q24 . 1 q24 . 3 ( Smac / DIABLO ) in TRAIL resistant cell lines . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
These inhibitors cause the accumulation of many proteins in the cell with the induction of apoptosis including TRAIL death receptors DR 4 and DR 5 , but the role of the TRAIL apoptotic pathway in proteasome inhibitor cytotoxicity is unknown . ^^^ Herein , we have demonstrated that the induction of apoptosis by the proteasome inhibitors , MG 132 and PS 341 ( bortezomib , Velcade ) , in primary CLL cells and the Burkitt lymphoma cell line , BJAB , is associated with up regulation of TRAIL and its death receptors , DR 4 and DR 5 . ^^^ Moreover , DR 4 : Fc or blockage of DR 4 and DR 5 expression using RNA interference , which prevents TRAIL apoptotic signaling , blocks proteasome inhibitor induced apoptosis . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
In our current report , we used DLD 1 colorectal cancer cells stably transfected with the POX gene under the control of a tetracycline inducible promoter and found POX stimulated expression of tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , DR 5 and cleavage of caspase 8 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
LT from HIV ( prog ) exhibited higher TRAIL and DR 5 mRNA levels than LT from HIV ( NP ) or controls . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Further , ASM deficient splenocytes fail to cluster DR 5 in ceramide enriched membrane domains upon TRAIL stimulation and resist TRAIL induced apoptosis , events that were restored by addition of natural C ( 16 ) ceramide . ^^^ Our data indicate that ceramide enriched membrane platforms are required for the signaling of TRAIL DR 5 complexes under physiological conditions . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) is a potential anticancer drug that selectively induces apoptosis in a variety of cancer cells by interacting with death receptors DR 4 and DR 5 . ^^^ The occurrence of DR 5 responsive tumor cells indicates that a DR 5 receptor specific TRAIL variant will permit tumor selective therapies . ^^^ By using the automatic design algorithm FOLD 10 , we successfully generated DR 5 selective TRAIL variants . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
CD4+ T cells expressed the TRAIL death receptor 5 ( DR 5 ) , upon HIV 1 binding to CD 4 . ^^^ The cultures were tested for expression of interferon alpha , TRAIL , DR 5 and apoptosis . ^^^ Inhibitors of IFNalpha , TRAIL , DR 5 and gp120 / CD4 binding were added to the cultures . ^^^ Antibodies against TRAIL and DR 5 partly inhibited apoptosis . ^^^ However , soluble CD 4 ( sCD 4 IgG ) efficiently blocked IFNalpha production , TRAIL and DR 5 expression and apoptosis of T helper cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
P glycoprotein enhances TRAIL triggered apoptosis in multidrug resistant cancer cells by interacting with the death receptor DR 5 . ^^^ Mechanistic analysis of TRAIL induced apoptosis in the MDR 1 transfected MCF 7 breast cancer cell line BC 19 revealed that TRAIL triggered significantly more apoptosis in these cells compared with parental MCF 7 cells by binding to the TRAIL receptor DR 5 . ^^^ DR 5 but not DR 4 engagement by TRAIL attenuated cellular ATP levels by robustly stimulating P gp ATPase activity , and thus triggered P gp dependent apoptosis by depletion of the cellular ATP pool . ^^^ P gp interacted with the TRAIL receptors DR 4 , DR 5 , and DcR 1 in plasma membranes and enhanced TRAIL binding to DR 5 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
TNF alpha markedly increased the expression of the proapoptotic receptor TRAIL R 2 . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Among the p 53 target genes , death receptor 5 ( DR 5 ) , which is the receptor for tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , showed the highest level of induction . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
PURPOSE : The proapoptotic receptors tumor necrosis factor related apoptosis inducing ligand receptor 1 ( TRAIL R 1 ) and TRAIL R 2 are targets of drugs in clinical development , and receptor expression levels may be important determinants of sensitivity to receptor agonists . ^^^ We assessed TRAIL R 1 and TRAIL R 2 expression patterns in a large cohort of melanomas and benign nevi . ^^^ RESULTS : TRAIL R 1 and TRAIL R 2 expression was higher in melanomas than in nevi ( P < 0 . 0001 ) , and higher in primary than in metastatic specimens ( P = 0 . 0031 and P < 0 . 0001 , respectively ) . ^^^ TRAIL R 1 and TRAIL R 2 expression exceeding the 95th percentile for nevi was found in 19 % and 74 % of melanoma specimens , respectively . ^^^ Although on univariate analysis , high TRAIL R 2 expression correlated with increased survival ( P = 0 . 0439 ) , it was not associated with survival within the primary or metastatic subcohorts . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumors sensitized to NK cell cytotoxicity showed a significant increase in surface expression of DR 5 [ tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) R 2 ; P < 0 . 05 ] ; in contrast , surface expression of MHC class 1 , MIC A / B , DR 4 ( TRAIL R 1 ) , and Fas ( CD 95 ) did not change . ^^^ The enhanced susceptibility to NK cell killing was completely abolished by blocking TRAIL on NK cells , and partially abolished by blocking DR 5 on tumor cells . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induces apoptosis in melanoma by interaction with death receptors TRAIL R 1 ( DR 4 ) or TRAIL R 2 ( DR 5 ) on melanoma cells or resists apoptosis by interaction with decoy receptors TRAIL R 3 ( DcR 1 ) or TRAIL R 4 ( DcR 2 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
IFN beta up regulated the expression of TRAIL , while NS 398 increased the expression of TRAIL receptors ( especially of death receptor 5 ) . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Deoxy Delta 12 , 14 prostaglandin J ( 2 ) induces death receptor 5 expression through mRNA stabilization independently of PPARgamma and potentiates TRAIL induced apoptosis . 15 Deoxy Delta ( 12 , 14 ) prostaglandin J ( 2 ) ( 15d PGJ ( 2 ) ) , the terminal derivative of the PGJ series , is emerging as a potent antineoplastic agent among cyclopentenone prostaglandins derivatives and also known as the endogenous ligand of peroxisome proliferator activated receptor gamma ( PPARgamma ) . ^^^ On the other hand , death receptor 5 ( DR 5 ) is a specific receptor for tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , which is one of the most promising candidates for new cancer therapeutics . ^^^ Here , we report that 15d PGJ ( 2 ) induces DR 5 expression at both mRNA and protein levels , resulting in the synergistic sensitization of TRAIL induced apoptosis in human neoplastic cells , such as Jurkat human leukemia cells or PC 3 human prostate cancer cells . 15d PGJ ( 2 ) significantly increased DR 5 mRNA stability , whereas it did not activate DR 5 promoter activity . ^^^ Moreover , a double stranded small interfering RNA targeting DR 5 gene , which suppressed DR 5 up regulation by 15d PGJ ( 2 ) , significantly attenuated apoptosis induced by cotreatment with 15d PGJ ( 2 ) and TRAIL . ^^^ These results suggest that 15d PGJ ( 2 ) is a potent sensitizer of TRAIL mediated cancer therapeutics through DR 5 up regulation . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
However , these cells did undergo apoptosis in response to another form of recombinant TRAIL , histidine tagged TRAIL , suggesting differing contributions of DR 4 and DR 5 in the response to these two forms of TRAIL . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) has been shown to induce apoptosis in prostate cancer cells through DR 4 and DR 5 death receptors , but not in normal prostate cells , which do not express these receptors . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Role of caspase 8 and DR 5 in TRAIL induced apoptosis of neuroblastoma cells ] . ^^^ This study investigated the role of caspase 8 and DR 5 in TRAIL induced apoptosis of NB cell line SKNDZ . ^^^ The SKNDZ cells expressing caspase 8 were not sensitive to TRAIL but those SKNDZ cells expressing both caspase 8 and DR 5 were sensitive . ^^^ CONCLUSIONS : SKNDZ cells expressing both caspase 8 and DR 5 restored the TRAIL sensitivity . ^^^ Caspase 8 and DR 5 play a key role in TRAIL induced apoptosis of NB cells . . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Differential inhibition of TRAIL mediated DR 5 DISC formation by decoy receptors 1 and 2 . ^^^ TRAIL induced apoptosis is mediated by the transmembrane receptors death receptor 4 ( DR 4 ) ( also known as TRAIL R 1 ) and DR 5 ( TRAIL R 2 ) . ^^^ In addition , DcR 1 and DcR 2 inhibit DR 4 and DR 5 mediated , TRAIL induced apoptosis and we demonstrate here that this occurs through distinct mechanisms . ^^^ While DcR 1 prevents the assembly of the death inducing signaling complex ( DISC ) by titrating TRAIL within lipid rafts , DcR 2 is corecruited with DR 5 within the DISC , where it inhibits initiator caspase activation . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
Therefore , the prognostic relevance was analyzed of the expression of TRAIL and its death receptors DR 4 and DR 5 on disease free survival and overall survival in stage 3 colon cancer patients treated with adjuvant chemotherapy . ^^^ METHODS : Tissue microarrays were constructed of primary tumor tissue from 376 stage 3 colon cancer patients treated in a randomized adjuvant chemotherapy study ( fluorouracil / levamisole 5 fluorouracil / levamisole / leucovorin ) and stained immunohistochemically for TRAIL , DR 4 , and DR 5 . ^^^ RESULTS : The majority of tumors showed high expression of TRAIL ( 83 % ) , DR 4 ( 92 % ) , and DR 5 ( 87 % ) . ^^^ TRAIL or DR 5 expression had no prognostic value . ^^^
Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and O14763	Pubmed	SVM Score :0.0
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