Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.66249624
Here we show that TRAIL R 1 can associate with TRAIL R 2 , suggesting that TRAIL may signal through heteroreceptor signaling complexes . 0.66249624^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.55034338
TRAIL induces apoptosis through its interaction with its two proapoptotic death receptors ( DRs ) , DR 4 and DR 5 . 0.55034338^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.51320445
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 ) . 0.51320445^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.63298387
TRAIL induces apoptosis by interacting with its receptors TRAIL R 1 and TRAIL R 2 . 0.63298387^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
We have isolated a new member of this family , designated Apo 2 ligand ( Apo 2L ) , via an expressed sequence tag . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 2 ligand ( Apo 2L ) / TNF related apoptosis inducing ligand , a new member of the TNF family , has been identified as an apoptosis inducing molecule . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 2 ligand ( Apo 2L ) is member of the tumor necrosis factor ligand family , and it induces apoptosis in cancer cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
BALB / c mammary adenocarcinoma cells engineered to express TNF related apoptosis inducing ligand ( TRAIL ) / APO 2 ligand ( APO 2L ) on their membrane ( TSA TRAIL ) grow with kinetics similar to that of parental cells ( TSA pc ) in vitro and in nu / nu mice . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
We now report that the colonization of MCF 10A cyclin D 1 transfectants was preferentially inhibited by gamma radiation and specific classes of apoptosis inducers [ Apo 2 ligand ( Apo 2L ) , but not tumor necrosis factor alpha ] . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
In present studies , treatment with tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL , also known as Apo 2 ligand [ Apo 2L ] ) is shown to induce apoptosis of the human acute leukemia HL 60 , U 937 , and Jurkat cells in a dose dependent manner , with the maximum effect seen following treatment of Jurkat cells with 0 . 25 microg / mL of Apo 2L ( 95 . 0 % + / 3 . 5 % of apoptotic 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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Activation of apoptosis by Apo 2 ligand is independent of FADD but blocked by CrmA . ^^^ A new member of the tumor necrosis factor ( TNF ) cytokine family , designated Apo 2 ligand ( Apo 21 ) [ 1 ] or TRAIL [ 2 ] , has been shown recently to induce apoptosis in various tumor cell lines ; however , its biological role is unknown . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 3 did not specifically bind to the Apo 2 ligand , suggesting the existence of a distinct ligand for Apo 3 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 2 ligand ( Apo2L [ 1 ] , also called TRAIL for tumor necrosis factor ( TNF ) related apoptosis inducing ligand [ 2 ] ) belongs to the TNF family and activates apoptosis in tumor cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL / Apo 2 ligand induced apoptosis in human T cells . ^^^ Recently , a new member of apoptosis inducing ligands , TRAIL ( TNF related apoptosis inducing ligand ) / Apo 2 ligand , was identified that might act in a similar way . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL ( APO 2 ligand ) and CD95L ( CD95 / APO 1 / Fas ligand ) share the highest homology among the TNF family members and the ability to induce apoptosis . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
APO 2 ligand : a novel lethal weapon against malignant glioma . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Involvement of APO 2 ligand / TRAIL in activation induced death of Jurkat and human peripheral blood T cells . ^^^ In the present work , we show that the cytotoxic cytokine APO 2 ligand ( APO2L ; also known as TRAIL ) is constitutively expressed as an intracytoplasmic protein in Jurkat T cells and derived sublines . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Safety and antitumor activity of recombinant soluble Apo 2 ligand . ^^^ Apo 2 ligand ( Apo2L , or TRAIL ) is a related molecule that triggers tumor cell apoptosis . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Activated human T cells release bioactive Fas ligand and APO 2 ligand in microvesicles . ^^^ Two known mediators of activation induced cell death are Fas ( CD 95 ) ligand ( FasL ) and APO 2 ligand ( APO2L ) / TNF related apoptosis inducing ligand ( TRAIL ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Control of apoptosis signaling by Apo 2 ligand . ^^^ Apo 2 ligand ( Apo2L , also called TRAIL ) is a member of the tumor necrosis factor ( TNF ) cytokine family . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Here , we report that the locoregional application of Apo 2 ligand ( Apo2L ) exerts strong antitumor activity on preestablished intracranially growing human U87MG glioma xenografts in athymic mice . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
APO 2 ligand ( APO2L ) / TRAIL is a novel member of the tumor necrosis factor cytokine family and a potent inducer of apoptosis in tumor cell lines . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL ( Apo 2 ligand ) and TWEAK ( Apo 3 ligand ) mediate CD4+ T cell killing of antigen presenting macrophages . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Lipopolysaccharide induces expression of APO 2 ligand / TRAIL in human monocytes and macrophages . ^^^ In this report , we show that human monocytes and monocyte derived macrophages stimulated with lipopolysaccharide ( LPS ) express APO 2 ligand ( APO2L , TRAIL ) , a recently discovered cytotoxic member of the TNF ligand superfamily . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
CD 59 cross linking induces secretion of APO 2 ligand in overactivated human T cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
In contrast to these Bcl 2 / Bag 1 interactions observed under serum starvation conditions , Bag 1 did not further enhance the strong protection from staurosporine , CD 95 ( Fas / Apo1 ) ligand , Apo 2 ligand ( TRAIL ) or chemotherapeutic drug induced apoptosis afforded by Bcl 2 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
The expression pattern of apoptosis related genes demonstrated the up regulation of both anti apoptotic factors such as the BCL 2 related protein A 1 , TRAF 3 , the inhibitor of apoptosis protein A 1 ( IAPI ) and apoptotic pathway elements such as Fas / Apo 1 , Apo 2 ligand etc . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) ( Apo 2 ligand [ Apo2L ] ) is a member of the TNF superfamily and has been shown to have selective antitumor activity . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ We found Apo 2 ligand ( Apo2L , also called TRAIL ) mRNA induction following gamma irradiation of Jurkat , MOLT 4 , CEM , and PBMC , all human T lineage derived cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Because tumour necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) ( Apo 2 ligand ) preferentially kills malignant cells while sparing normal cells , it may be therapeutically useful against cancers , including those of haematopoietic origin . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
One promising experimental strategy to target glioma is the employment of death ligands such as CD 95 ( Fas / Apo1 ) ligand or Apo 2 ligand ( TRAIL ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL ( TNF related apoptosis inducing ligand ) which is also known as Apo 2 ligand ( Apo2L ) , a new member of TNF family , can induce apoptosis in some tumor cells but not in many normal cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
In contrast , DcR 3 does not confer protection from the death ligand Apo 2 ligand ( TRAIL ) . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Apo 2 ligand ( Apo2L , also TRAIL ) induction was one of the earliest events following IFN administration in U 266 cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Differential secretion of Fas ligand or APO 2 ligand / TNF related apoptosis inducing ligand carrying microvesicles during activation induced death of human T cells . ^^^ Preformed Fas ligand ( FasL ) and APO 2 ligand ( APO2L ) / TNF related apoptosis inducing ligand ( TRAIL ) are stored in the cytoplasm of the human Jurkat T cell line and of normal human T cell blasts . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
These biological response modifiers include monoclonal antibodies such as rituximab ( Rituxan ; Genentech , Inc , South San Francisco , CA , and IDEC Pharmaceuticals , San Diego , CA ) that alter signal transduction pathways , cytokines such as TRAIL ( Apo 2 ligand ) , ligands for retinoid / steroid family nuclear receptors , and small molecule compounds that bind and inhibit protein kinases . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Treatment of colon tumor cells deficient in DNA mismatch repair with the death receptor ligand apo 2 ligand ( Apo2L ) / tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) selected in vitro or in vivo for refractory subclones with Bax frameshift mutations including deletions at a novel site . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor related apoptosis inducing ligand ( Apo 2 ligand ) in vivo . ^^^ In contrast , alpha TOS showed a more profound antitumor effect , at both the level of inhibition of proliferation and induction of tumor cell apoptosis . alpha TOS was nontoxic to normal cells and tissues , triggered apoptosis in p 53 ( / ) and p 21 ( Waf1 / Cip1 ( / ) ) cancer cells , and exerted a cooperative proapoptotic activity with tumor necrosis factor related apoptosis inducing ligand ( Apo 2 ligand ) due to differences in proapoptotic signaling . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL ( Apo 2 ligand ) is a member of the tumor necrosis factor ( TNF ) family of cytokines that induces apoptosis . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Induction and regulation of tumor necrosis factor related apoptosis inducing ligand / Apo 2 ligand mediated apoptosis in renal cell carcinoma . ^^^ The tumor necrosis factor family member tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) / Apo 2 ligand induces apoptosis in a variety of tumor cell types , while having little cytotoxic activity against normal cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Tumor infiltrating CD4+ T lymphocytes express APO 2 ligand ( APO2L ) / TRAIL upon specific stimulation with autologous lung carcinoma cells : role of IFN alpha on APO2L / TRAIL expression and mediated cytotoxicity . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL , Apo 2 ligand ) effectively kills multiple myeloma ( MM ) cells in vitro irrespective of refractoriness to dexamethasone and chemotherapy . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 2 ligand ( Apo2L / TRAIL ) is a member of the tumor necrosis factor ( TNF ) cytokine family . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
X linked inhibitor of apoptosis ( XIAP ) blocks Apo 2 ligand / tumor necrosis factor related apoptosis inducing ligand mediated apoptosis of prostate cancer cells in the presence of mitochondrial activation : sensitization by overexpression of second mitochondria derived activator of caspase / direct IAP binding protein with low pl ( Smac / DIABLO ) . ^^^ The resistance to Apo 2 ligand ( Apo2L ) / tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) mediated apoptosis could be overcome by treatment with subtoxic concentrations of actinomycin D ( Act D ) in prostate tumor cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 2 ligand or tumour necrosis factor related apoptosis inducing ligand ( Apo2L / TRAIL ) is one of the several members of the tumour necrosis factor ( TNF ) gene superfamily that induce apoptosis through engagement of death receptors ( DRs ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 2 ligand or tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( Apo2L / TRAIL ) is one of several members of the TNF gene superfamily that induce apoptosis through engagement of death receptors . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 2 ligand ( Apo2L , also known as TRAIL ) is a member of the tumour necrosis factor ( TNF ) family of cytokines that selectively induces the death of cancer cells , but not of normal cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apoptosis induction in prostate cancer cells and xenografts by combined treatment with Apo 2 ligand / tumor necrosis factor related apoptosis inducing ligand and CPT 11 . ^^^ LNCaP derived C 4 2 human prostate cancer cells are quite resistant to treatment with Apo 2 ligand ( Apo2L ) or tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , when using a nontagged , Zn bound recombinant trimeric version that is devoid of any exogeneous sequences and therefore least likely to be immunogenic in human patients and that has been optimized for maximum efficacy and minimum toxicity . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apo 2 Ligand or Tumour Necrosis Factor ( TNF ) Related Apoptosis Inducing Ligand ( Apo2L / TRAIL ) is a member of the TNF gene superfamily that selectively induces apoptosis in tumor cells of diverse origins through engagement of death receptors . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand or Apo 2 ligand ( TRAIL / Apo2L ) is a member of the tumor necrosis factor ( TNF ) family of ligands capable of initiating apoptosis through engagement of its death receptors . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Interactions between histone deacetylase ( HDAC ) inhibitors and tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , also known as Apo 2 ligand , were examined in human leukemia cells ( e . g . , U 937 , Jurkat , and HL 60 ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
In the present study , we analyzed the expression and secretion of FasL and APO 2 ligand ( APO2L ) / TRAIL in the human melanoma cell line MelJuSo . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Resistance to Apo 2 ligand ( Apo2L ) / tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) mediated apoptosis and constitutive expression of Apo2L / TRAIL in human T cell leukemia virus type 1 infected T cell lines . ^^^ Apo 2 ligand ( Apo2L ; also tumor necrosis factor related apoptosis inducing ligand [ TRAIL ] ) has been implicated in antitumor therapy . ^^^
Interacting proteins: P50591 and O00220	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 ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Dengue virus induced apoptosis in hepatic cells is partly mediated by Apo 2 ligand / tumour necrosis factor related apoptosis inducing ligand . ^^^ In this work , DEN type 2 ( DEN 2 ) strain NGC was shown to induce apoptosis in the hepatic cell line HepG 2 , and infection of HepG 2 cells was found to induce Apo 2 ligand ( Apo2L , also known as tumour necrosis factor related apoptosis inducing ligand or TRAIL ) expression . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL ( Apo 2 ligand ) described as a type 2 transmembrane protein belonging to the TNF superfamily can induce apoptotic cell death in a variety of cell types . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
In parallel , VA strongly augmented the effect of TNF related apoptosis inducing ligand ( TRAIL or Apo 2 ligand ) on HepG 2 cells ( 10 % vs . 58 % apoptosis ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
APO 2 ligand / tumor necrosis factor related apoptosis inducing ligand in prostate cancer therapy . ^^^ Apo 2 ligand ( Apo2L ) , also called Tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) , is one of several members of the TNF gene superfamily that induces apoptosis through engagement of death receptors . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
To examine the efficacy of recombinant soluble Apo 2 ligand ( Apo2L ) / tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) against breast cancer growth in bone , we established a mouse model in which MDA MB 231 human breast cancer cells were transplanted directly into the marrow cavity of the tibiae of athymic nude mice producing osteolytic lesions in the area of injection . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Multiple mechanisms underlie resistance of leukemia cells to Apo 2 Ligand / TRAIL . ^^^ To investigate the basis for resistance of leukemia cells to the zinc bound form of Apo 2 ligand ( Apo2L ) / TRAIL , which is currently being evaluated in clinical trial , we isolated several resistant HL 60 clones from parental HL 60 cells by selection using the recombinant Apo2L / TRAIL . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
TNF related apoptosis inducing ligand ( TRAIL ) is a typical member of the tumor necrosis factor ( TNF ) ligand family that is expressed as a type 2 membrane protein ( memTRAIL ) and signals apoptosis via the death domain containing receptors TRAIL R 1 and 2 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Inhibition of PI 3 kinase with the chemical inhibitor wortmannin increased TNF related apoptosis inducing ligand ( TRAIL ; Apo 2 ) mRNA and protein expression . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Virol . 65 : 4114 4123 , 1991 ) , TNF related apoptosis inducing ligand receptors ( TRAIL R 1 and R 2 ) ( C . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Apoptosis in BxPC 3 cells mediated by TNF related apoptosis inducing ligand ( TRAIL ) and CD95L was likewise increased 2 . 3 + / 0 . 5 fold and 7 . 4 + / 2 . 5 fold , respectively . sst 2 dependent activation and cell sensitization to death ligand induced apoptosis involved activation of the executioner caspases , key factors in both death ligand or mitochondria mediated apoptosis . sst 2 affected both pathways : first , by up regulating expression of TRAIL and TNFalpha receptors , DR 4 and TNFRI , respectively , and sensitizing the cells to death ligand induced initiator capase 8 activation , and , second , by down regulating expression of the antiapoptotic mitochondrial Bcl 2 protein . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Our results show , that the exposure of three metastatic melanoma cell lines ( A 2058 , SK Mel 5 , and WM 266 4 ) to recombinant TIMP 3 , N terminal MMP inhibitory domain of TIMP 3 , as well as to adenovirally expressed TIMP 3 results in stabilization of tumor necrosis factor receptor 1 ( TNF RI ) , FAS , and TNF related apoptosis inducing ligand receptor 1 ( TRAIL RI ) on melanoma cell surface and sensitizes these cells to apoptosis induced by TNF alpha , anti Fas antibody and TRAIL . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
To date , at least five cell death ligand receptor systems [ tumor necrosis factor ( TNF ) alpha and receptors , Fas ( also called APO 1 / CD95 ) ligand and receptors , TNF related apoptosis inducing ligand ( TRAIL ; also called APO 2 ) and receptors , APO 3 ligand and receptors , and PFG 5 ligand and receptors ] have been reported in granulosa cells of porcine ovaries . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
To examine whether the combination of TNF related apoptosis inducing ligand ( TRAIL ) treatment and cancer cell selective expression of the TRAIL death receptor could induce cell death in TRAIL resistant cancer cells , we generated a death receptor 4 ( DR 4 ) expressing adenovirus ( Ad hTERT DR 4 ) , in which the expression of DR 4 is driven by the hTERT promoter . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
The expression of FasL , Fas , TNF related apoptosis inducing ligand ( TRAIL ) and TRAIL R 1 on erythroblasts decreased significantly during thalidomide treatment . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
TRAIL , also called Apo2L , is a cytotoxic protein that induces apoptosis of many transformed cell lines but not of normal tissues , even though its death domain containing receptor , DR 4 , is expressed on both cell types . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
The human receptor for TRAIL was found to be an undescribed member of the TNF receptor family ( designated death receptor 4 , DR 4 ) that contains a cytoplasmic `` death domain ' ' capable of engaging the cell suicide apparatus but not the nuclear factor kappa B pathway in the system studied . ^^^ Thus , the DR 4 TRAIL axis defines another receptor ligand pair involved in regulating cell suicide and tissue homeostasis . . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Using a soluble molecule containing the TRICK 2 extracellular domain , we demonstrated that TRICK 2 , like DR 4 [ 1 ] , is a receptor for TRAIL / APO 2L [ 2 , 3 ] and could inhibit TRAIL induced killing of lymphocyte lines , such as the Jurkat T cell line . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Based on homology searching of a private database , a receptor for TRAIL ( DR 4 or TRAIL R 1 ) was recently identified . ^^^ Like TRAIL R 1 , TRAIL R 2 engages a caspase dependent apoptotic pathway but , in contrast to TRAIL R 1 , TRAIL R 2 mediates apoptosis via the intracellular adaptor molecule FADD / MORT1 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL R 3 encodes a 299 amino acid protein with 58 and 54 % overall identity to TRAIL R 1 and R 2 , respectively . ^^^ In contrast to TRAIL R 1 and R 2 , this receptor shows restricted expression , with transcripts detectable only in peripheral blood lymphocytes and spleen . ^^^ Moreover , unlike TRAIL R 1 and R 2 , in a transient overexpression system TRAIL R 3 does not induce apoptosis . . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Death receptor 4 ( DR 4 ) is a recently described receptor for the cytotoxic ligand TRAIL that reportedly uses a FADD independent pathway to induce apoptosis and does not activate the NF kappaB pathway . ^^^ Death receptor 4 ( DR 4 ) is a recently described receptor for the cytotoxic ligand TRAIL that reportedly uses a FADD independent pathway to induce apoptosis and does not activate the NF kappaB pathway . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Both DR 4 and KILLER / DR5 independently bind to their specific ligand TRAIL and engage the caspase cascade to induce apoptosis . ^^^ TRID ( also known as TRAIL R 3 ) is an antiapoptotic decoy receptor that lacks the cytoplasmic death domain and competes with KILLER / DR5 and DR 4 for binding to TRAIL . ^^^ Unlike KILLER / DR5 , none of the other KILLER / DR5 family members , including DR 4 , TRID , or the ligand TRAIL , displayed genotoxic stress or TNF alpha regulation in a p 53 transcription dependent manner . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
A human receptor for the cytotoxic ligand TRAIL ( TRAIL receptor 1 , designated DR 4 ) was identified recently as a member of the tumor necrosis factor receptor family . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL R 2 is structurally similar to the death domain containing receptor TRAIL R 1 ( DR 4 ) , and is capable of inducing apoptosis . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
The specificity of the mAb permitted a precise evaluation of the TRAIL receptors that induce apoptosis ( TRAIL R 1 and R 2 ) compared with the TRAIL receptors that potentially regulate TRAIL mediated apoptosis ( TRAIL R 3 and R 4 ) . ^^^ Immobilized anti TRAIL R 1 or R 2 mAbs were cytotoxic to TRAIL sensitive tumor cells , whereas tumor cells resistant to recombinant TRAIL were also resistant to these mAbs and only became sensitive when cultured with actinomycin D . ^^^ The anti TRAIL R 1 and R 2 mAb induced death was characterized by the activation of intracellular caspases , which could be blocked by carbobenzyloxy Val Ala Asp ( OMe ) fluoromethyl ketone ( zVAD fmk ) and carbobenzyloxy Ile Glu ( OMe ) Thr Asp ( OMe ) fluoromethyl ketone ( zIETD fmk ) . ^^^ 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 O00220	Pubmed	SVM Score :0.0
Recently , TRAIL has been demonstrated to selectively induce apoptosis in transformed cell lines , and subsequently four receptors ( TRAIL R 1 TRAIL R 4 ) have been identified . ^^^ 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 . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ DR 4 mRNA was present only in THP 1 cells and was the only TRAIL R transcript increased by IFN gamma . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
MK is highly homologous and binds TRAIL with similar affinity as human DR 4 and KILLER / DR5 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
CMV infection increased the expression of TRAIL R 1 and R 2 , whereas IFN gamma down regulated the expression of TRAIL Rs on uninfected fibroblasts . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
In transfection experiments c E 10 oligomerizes , binds to the cytoplasmic portion of TRAIL receptor 1 ( DR 4 ) and coprecipitates with TRADD . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 . ^^^ JNK activation by TRAIL R 1 is mediated by a TRAF 2 MEKK1 MKK 4 but not the TRAF 2 NIK / IkappaB kinase alpha / beta signaling pathway . ^^^ We also show that activation of NF kappaB or overexpression of TRAIL R 4 does not protect TRAIL R 1 induced apoptosis . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
Biochemical analysis of the signaling events induced by TRAIL revealed that PK could be sensitized for TRAIL and , similarly , for TRAIL R 1 and TRAIL R 2 specific apoptosis by pretreatment of the cells with cycloheximide ( CHX ) . ^^^
Interacting proteins: P50591 and O00220	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 ) . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ In the present studies , we identified a subgroup of TRAIL resistant cancer cell lines characterized by low or absent basal DR 4 or high expression of the caspase activation inhibitor FLIP . ^^^ Four of five TRAIL sensitive cell lines expressed high levels of DR 4 mRNA and protein , whereas six of six TRAIL resistant cell lines expressed low or undetectable levels of DR 4 ( chi 2 ; P < 0 . 01 ) . ^^^ Two TRAIL resistant lines that expressed DR 4 contained an A to G alteration in the death domain encoding arginine instead of lysine at codon 441 . ^^^ These results suggest that the major determinants for TRAIL sensitivity may be the expression level of DR 4 and FLIP . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
WAF1 / CIP1 ) inhibits initiator caspase cleavage by TRAIL death receptor DR 4 . ^^^ Here we show that overexpression of the cytoplasmic domain ( CD ) of the DR 4 TRAIL receptor ( TNFRSF10A , TRAIL R 1 ) in human breast , lung , and colon cancer cell lines , using an adenovirus vector ( Ad DR 4 CD ) , leads to p 53 independent apoptotic cell death involving cleavage of CASP 8 and 10 proximally and CASP 3 , 6 , and 7 distally . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
We show that the death receptors TRAIL R 1 and R 2 are located in the trans Golgi network , whereas the inhibitory receptors TRAIL R 3 and R 4 are located in the nucleus . ^^^ After exposure to TRAIL , TRAIL R 1 and R 2 are internalized into endosomes , whereas TRAIL R 3 and R 4 undergo relocation from the nucleus to the cytoplasm and cell membranes . ^^^ This movement of decoy receptors was dependent on signals from TRAIL R 1 and R 2 , as shown by blocking experiments with Abs to TRAIL R 1 and R 2 . ^^^ The location of TRAIL R 1 , R 3 , and R 4 in melanoma cells transfected with cDNA for these receptors was similar to that in nontransfected cells . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ Taken together , our data suggest that TRAIL R 1 responds to either cross linked or non cross linked sTRAIL which signals NF kappaB activation and apoptosis , whereas TRAIL R 2 signals NF kappaB activation , apoptosis , and JNK activation only in response to cross linked TRAIL . . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
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 O00220	Pubmed	SVM Score :0.0
The induction of apoptosis by TRAIL in PC 3 cells was mediated by a death receptor , DR 4 , and the downstream caspases . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
The cytotoxic ligand TRAIL interacts with five receptors , only two of which ( TRAIL R 1 and R 2 ) have a death domain . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Homozygous deletion of the death receptor DR 4 gene in a nasopharyngeal cancer cell line is associated with TRAIL resistance . ^^^ 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 . ^^^ The deletion of DR 4 in FaDu cells is associated with resistance to the cytotoxic effects of TRAIL . ^^^ Re introduction of wild type DR 4 leads to apoptosis and restores TRAIL sensitivity of FaDu cells . ^^^ These observations suggest that the death inducing DR 4 receptor gene may be a rare target for inactivation in human cancer and that DR 4 loss may contribute to resistance to TRAIL therapy . . ^^^
Interacting proteins: P50591 and O00220	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 ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Substitution of the C terminal region of IKKgamma , which interacts with RIP , with a truncated DR 4 lacking its cytoplasmic death domain , produced a molecule that could induce IKK and NF kappaB activation in cells in response to TRAIL . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Other members of the TNFR superfamily , including TRAIL receptor 1 and CD 40 , show similar homotypic association . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ TRAIL R 1 , R 2 , and R 4 were expressed in 6 HCC cell lines examined , but TRAIL R 3 was expressed in only 2 of the 6 cell lines . ^^^ In addition , immunohistochemical results revealed a high and prevalent expression of TRAIL R 1 and R 2 in human HCC tissues . ^^^ Despite the expression of TRAIL R 1 and R 2 , all 6 HCC cell lines showed resistance to TRAIL induced apoptosis with no relation to nuclear factor kappa B ( NF kappaB ) levels induced by TRAIL . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
As yet , four TRAIL receptors have been cloned , two of which ( TRAIL R 1 and 2 ) bear a death domain and mediate apoptosis , whereas two others ( TRAIL R 3 and 4 ) lack ( functional ) death domains and are supposed to act as decoy receptors . ^^^
Interacting proteins: P50591 and O00220	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 ) . ^^^ 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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
We previously identified a major subgroup of TRAIL resistant cancer cell lines with absent , or reduced DR 4 expression containing a K441R polymorphism or harboring elevated levels of the caspase activation inhibitor FLIP . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Cotreatment with the caspase 8 inhibitor z IETD fmk or DR 4 : Fc significantly inhibited Apo 2L / TRAIL induced apoptosis . ^^^ 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 . . ^^^ 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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
Moreover , the cytotoxicity of IR plus TRAIL observed in erythroleukemic cells was accompanied by the selective up regulation of the surface expression of TRAIL R 1 ( DR 4 ) , and it was completely blocked by the z Val Ala Asp ( OMe ) CH ( 2 ) ( z VAD fmk ) caspase inhibitor . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 . ^^^ To confirm this hypothesis , we demonstrated that soluble DR 4 Fc fusion protein , a TRAIL pathway inhibitor , inhibited IFN gamma induced cell death in SNU 368 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
BACKGROUND AND AIMS : Programmed cell death via the Fas receptor / Fas Ligand and DR 4 , DR5 / TRAIL plays a major role in tumor escape and elimination mechanisms . ^^^ METHODS : Five pancreatic cell lines were investigated for the expression of FasL / Fas , DcR 3 , DR 4 , DR5 / TRAIL , DcR 1 , DcR 2 , and other death pathways related molecules such as Bax , bcl xL , bcl 2 , FADD , and caspase 3 by flow cytometry , immunoblotting , and RT / PCR , both semiquantitative and real time ( TaqMan ) . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
DR 4 ( TRAIL R 1 ) , a member of the tumor necrosis factor receptor superfamily , is a cell surface receptor that triggers the apoptotic machinery upon binding to its ligand tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^ 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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
Nucleotide substitution in the ectodomain of trail receptor DR 4 is associated with lung cancer and head and neck cancer . ^^^ The tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors , including proapoptotic DR 4 and KILLER / DR5 , are located on 8p21 22 . ^^^ 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 O00220	Pubmed	SVM Score :0.0
Molecular abnormalities accompanying repressed NF kappaB activity included failure to induce TNF RII receptor together with enhanced levels of TRAIL death receptor 4 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Elevated expression of TRAIL and of death receptor 4 ( DR 4 ) protein was identified at the involution stage of normal mammary glands as well as at the lactation stage of the IL 10 transgenic mice . ^^^ These results indicate that the elevated expression of IL 10 at the involution stage recruits lymphocytes and induces the expression of TRAIL and DR 4 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NF kappaB activation was mediated by the death receptors , TRAIL R 1 and R 2 , but not by TRAIL R 3 or R 4 and was only observed in HeLa cells in the presence of z VAD . fmk . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
GCDC treatment increased expression of TRAIL R2 / DR5 mRNA and protein 10 fold while expression of TRAIL R 1 was unchanged . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ RID induces the internalization of TRAIL R 1 from the cell surface , as shown by flow cytometry and indirect immunofluorescence for TRAIL R 1 . ^^^ TRAIL R 1 was internalized in distinct vesicles which are very likely to be endosomes and lysosomes . ^^^ TRAIL R 1 is degraded , as indicated by the disappearance of the TRAIL R 1 immunofluorescence signal . ^^^ Inhibition of TRAIL induced apoptosis and forced internalization of TRAIL receptor 1 by adenovirus proteins . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Four cell lines ( two sensitive ) and five primary tumours ( two sensitive ) demonstrated mRNA expression of the intra cellular death domain containing TRAIL R 1 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Human herpesvirus 7 induces the functional up regulation of tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) coupled to TRAIL R 1 down modulation in CD 4 ( + ) T cells . ^^^ 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 . ^^^ Of note , the down regulation of TRAIL R 1 selectively occurred in cells coexpressing HHV 7 antigens that became resistant to TRAIL mediated cytotoxicity . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
Of the 8 tumors that were cured , Fas was expressed in 3 ( 38 % ) , TRAIL R 1 in 6 ( 75 % ) and tumor necrosis factor ( TNF ) R 1 in 8 ( 100 % ) , whereas these pro apoptotic receptors were present in only 1 ( 14 % ) , 1 ( 14 % ) , and 4 ( 57 % ) of the 7 tumors that went on to recur , respectively . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
We have found TRAIL R 1 and R 2 death receptor , and TRAIL R 3 and R 4 decoy receptor mRNA expression in most of the 57 B CLL patients studied ( R 1 82 % , R 2 100 % , R 3 96 % and R 4 82 % ) . ^^^ TRAIL R 1 and R 2 proteins were expressed on the surface and within the cells , whereas R 3 and R 4 decoy receptors were almost exclusively expressed in the cytoplasm . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
RESULTS : Treatment with suboptimal concentrations of etoposide or doxorubicin rendered T 47D cells sensitive to anti Fas antibody or TRAIL , consistent with Fas and TRAIL R 1 mRNA expression by T 47D cells following drug treatment . ^^^ In contrast , neither drug sensitized MCF 7 cells to TRAIL or anti Fas antibody , most likely due to diminished Fas and TRAIL R 1 expression following drug treatment . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 . ^^^ 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 O00220	Pubmed	SVM Score :0.0
Both IFN beta and gamma irradiation induce apoptosis through the extrinsic , receptor mediated pathway , IFN beta through TRAIL , radiation through DR 4 , and both through caspase 8 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
TG selectively upregulated DR 5 but had no effect on the expression of the other TRAIL receptor , DR 4 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Death receptor 4 ( DR 4 ; also called TRAIL R 1 ) , a member of the tumor necrosis factor receptor superfamily , is a cell surface receptor that triggers the apoptotic machinery upon binding to its ligand tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^ Death receptor 4 ( DR 4 ; also called TRAIL R 1 ) , a member of the tumor necrosis factor receptor superfamily , is a cell surface receptor that triggers the apoptotic machinery upon binding to its ligand tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ Cisplatin showed synergistic effect on TRAIL induced apoptosis in most HCC cell lines regardless of their p 53 status and TRAIL R 1 was induced by cisplatin treatment in certain cell lines . ^^^ 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 O00220	Pubmed	SVM Score :0.0
TRAIL ( Apo 2 L ) and Apo 3 L are capable of inducing cell death via their receptors Trail R 1 to Trail R 4 and TRAMP . ^^^ Immunohistochemistry of epiretinal membranes of traumatic PVR was performed for the detection of TRAIL and Trail R 1 . ^^^ Protein expression of Trail R 1 was examined in cultured human RPE cells by western blot . ^^^ 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 . ^^^ Immunohistochemical studies on PVR membranes identified TRAIL and Trail R 1 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
The tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors TRAIL R 1 , R 2 , R 3 and R 4 are located on 8p21 p 22 and might be candidate tumor suppressor genes in this region . ^^^ 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 . ^^^ Overall , we detected 1 , 11 and 3 alterations in the TRAIL R 1 , R 2 and R 4 genes , respectively . ^^^ 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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
All four TRAIL receptors ( TRAIL R 1 through TRAIL R 4 ) are expressed in these cell lines . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Moreover , experiments performed using agonistic polyclonal antibodies , which mimic the interactions between TRAIL and each TRAIL receptor , indicated that TRAIL R 1 was responsible for mediating the TRAIL induced maturation . ^^^
Interacting proteins: P50591 and O00220	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 ) . ^^^ TRAIL induced and DR 4 mediated apoptosis in Jurkat cells is independent of DAP3 . . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
Some human diseases are associated with excess or deficient rates of apoptosis , and therapeutic strategies to regulate the rate of apoptosis include inhibition or activation of caspases , mRNA antisense to reduce anti apoptotic factors like Bcl 2 and survivin and recombinant TRAIL to activate pro apoptotic receptors , DR 4 and DR5 . . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
Expression of TRAIL and TRAIL receptors in colon carcinoma : TRAIL R 1 is an independent prognostic parameter . ^^^ 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 ) . ^^^ CONCLUSIONS : TRAIL R 1 is an independent prognostic factor in R 0 resected Unio Internationale Contra Cancrum stage II / III colon cancer . . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
METHODS : The expression of TRAIL and TRAIL R 1 , 2 , 3 and 4 in lymphocytic sialadenitis was examined by immunoperoxidase staining in patients with Sjgren ' s syndrome and in normal subjects . ^^^ To elucidate the mechanism of de novo expression of TRAIL R 1 antigen , we quantitatively investigated its induction by cytokines in human salivary duct cell line ( HSG ) by cell enzyme linked immunosorbent assay . ^^^ In patients with severe lymphocytic sialadenitis , TRAIL R 1 , TRAIL R 2 , or both were strongly expressed on the ductal epithelial cells . ^^^ In contrast , TRAIL R 1 and R 2 were not found in the minor salivary glands of normal subjects or patients with mild lymphocytic sialadenitis . ^^^ Unstimulated HSG cells did not express TRAIL R 1 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
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 O00220	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 O00220	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 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 O00220	Pubmed	SVM Score :0.0
A significantly positive correlation was observed between caspase 3 activity and TRAIL R 1 , R 2 . ^^^ Caspase 3 activity and TRAIL R 1 , R 2 expression in tumor tissue were significantly lower than those in non tumor tissue in HBV related HCC . ^^^ Some HCV related HCC cases , however , demonstrated elevated caspase 3 activity and TRAIL R 1 , R 2 expression in tumor tissue . ^^^ Both TRAIL R 1 and R 2 showed coefficient correlation with caspase 3 activity , and were strongly associated with apoptosis in human HCC . . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
METHODS AND RESULTS : The role of TRAIL / TRAIL Rs in vascular biology was investigated in primary human umbilical vein endothelial cells ( HUVECs ) and aortic endothelial cells , which showed comparable surface expression of death ( TRAIL R 1 and R 2 ) and decoy ( TRAIL R 3 and R 4 ) TRAIL Rs . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
The expression levels of DR 4 and the decoy receptors , DcR 1 and DcR 2 , did not correlate with TRAIL sensitivities . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL Receptor 1 ( TRAIL R 1 ) was expressed in TRAIL sensitive HTB 92 and HTB 93 cell lines , but not in TRAIL resistant HTB 91 and HTB 94 cells . ^^^ HTB 82 cells , which expressed the long ( c FLIP ( L ) ) and short ( c FLIP ( S ) ) splice variants of the FLICE like inhibitory protein ( FLIP ) , were resistant to TRAIL in spite of the presence of TRAIL R 1 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
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 . ^^^ Preparation and characterization of a set of monoclonal antibodies to TRAIL and TRAIL receptors DR 4 , DR 5 , DcR 1 , and DcR 2 . ^^^ 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 O00220	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 O00220	Pubmed	SVM Score :0.0
By employing receptor specific blocking antibodies we demonstrate that TRAIL receptor 1 plays the primary role in mediating caspase activation and apoptosis in HaCaT cells . ^^^ Taken together , our data suggest that beside its potent pro apoptotic role , LZ TRAIL leads to pro inflammatory responses that are mainly mediated by TRAIL receptor 1 in HaCaT keratinocytes . . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
All cell lines expressed the death receptor ( DR ) 5 TRAIL receptor , whereas expression of DR 4 was more variable . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
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 . ^^^ In contrast , RA synoviocytes did not show increased expression of TRAIL R 1 ( DR 4 ) , nor was there any difference in expression of Fas between RA and osteoarthritis synovial cells . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
In this study , we report that endothelial cells ( EC ) , isolated from human umbilical veins or human dermal microvessels , express death domain containing TRAIL R 1 and R 2 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
An antibody against DR 4 ( TRAIL R 1 ) in combination with doxorubicin selectively kills malignant but not normal prostate cells . ^^^ There was no correlation between TRAIL phenotype and expression of c FLIP , caspases or TRAIL decoy receptors , although PrSC failed to express DR 4 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Surface expression of TRAIL receptors DR 4 and DR 5 was analysed by FACS . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 . ^^^ Both anti TRAIL R 1 mAbs and anti TRAIL R2mAbs also caused cell death in hepatocytes . ^^^ 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 O00220	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 O00220	Pubmed	SVM Score :0.0
OBJECTIVE : To characterize the expression pattern of tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) and its cognate receptors ( TRAIL R 1 , R 2 , R 3 , and R 4 ) on rheumatoid arthritis ( RA ) synovial fluid ( SF ) lymphocytes and monocyte / macrophages and on cultured RA synovial fibroblasts . ^^^ In contrast , RA SF macrophages expressed TRAIL R 3 , a decoy receptor ( P < 0 . 01 versus isotype control ) , but not TRAIL , or TRAIL R 1 , R 2 , or R 4 . ^^^ Adenoviral mediated delivery of TRAIL had no effect on the survival of normal macrophages or RA synovial fibroblasts but readily induced apoptosis in the prostate cancer cell line ( PC 3 ) that expressed TRAIL R 1 and R 2 . ^^^ CONCLUSION : TRAIL R 1 and R 2 , which are required for signal transmission by TRAIL , were not detected on RA SF lymphocytes , macrophages , or synovial fibroblasts . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
TNF R 1 ( p 55 ) , TRAIL receptor 1 and 2 ( DR 4 and 5 ) , and Fas were expressed ; RANK was undetectable . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
Expression of TRAIL receptor 1 ( TRAIL R 1 ) , FLICE inhibitory protein ( Fas associating protein with death domain like interleukin 1 converting enzyme ) , and Bcl 2 was assessed by Western blot . ^^^ 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 . ^^^ Expression of TRAIL R 1 , FLIPL , and Bcl 2 did not account for the apoptosis by the combined treatment of TRAIL with ActD . ^^^ CONCLUSIONS : Although TRAIL R 1 was constitutively expressed ; cultured synovial fibroblasts were resistant to apoptosis by TRAIL . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
DR 4 , and TRAIL R2 / DR5 ) are involved in immune mediated neutralization of activated or autoreactive lymphocytes , virus infected cells , and tumor cells . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
To reveal the molecular mechanism of selective follicular atresia in porcine ovaries , we investigated the changes in the expression of tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) and its receptor ( DR 4 ) proteins and TRAIL mRNA in granulosa cells during follicular atresia . ^^^ Immunohistochemical , Western immunoblotting and reverse transcription polymerase chain reaction analyses ( RT PCR ) revealed that significant increases in TRAIL protein and mRNA levels but not DR 4 protein were changed during atresia . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
TRAIL R 1 , however , was never expressed at any time point examined , whereas the expression of TRAIL R 4 , which showed a progressive increase in CD 8 ( + ) T cells , remained constant in NK cells . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
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 O00220	Pubmed	SVM Score :0.0
DR 4 was not recruited to the DISC upon TRAIL treatment , and caspase 8 was not activated at the DISC . ^^^ Although total cellular DR 4 mRNA and protein were virtually identical in TRAIL sensitive parental and TRAIL resistant clones , DR 4 protein expression on the cell surface was essentially undetectable in the TRAIL resistant clones . ^^^ 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 O00220	Pubmed	SVM Score :0.0
Spontaneous apoptosis ( SA ) and apoptosis markers Fas associated death domain like IL 1 beta converting enzyme ( FLICE ) like inhibitory protein ( FLIP ) , Bcl 2 , TRAIL ( tumor necrosis factor related apoptosis inducing ligand ) , TRAIL receptor 1 , and Fas were determined in 55 HIV 1 infected persons treated with highly active antiretroviral therapy ( HAART ) for 48 months . ^^^ Increased SA of peripheral blood mononuclear cells ( PBMCs ) and CD 8 T lymphocytes and increased TRAIL receptor 1 expression strongly predicted a poorer recovery of CD 4 T cell count . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
OCs overexpressed TRAIL decoy receptor DcR 2 in the presence of MM T cells and death receptor DR 4 in T cell depleted cultures . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
In addition , Btk is phosphorylated by SCF , which causes association of Btk with TRAIL receptor 1 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL mediates its effect via death receptors 4 ( DR 4 ) and DR 5 and appears to selectively induce apoptosis in cancer cells . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Death receptor 4 ( DR 4 ) is one of the tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors and triggers apoptosis on ligation with TRAIL or overexpression . ^^^ Death receptor 4 ( DR 4 ) is one of the tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) receptors and triggers apoptosis on ligation with TRAIL or overexpression . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
Death receptor 4 ( DR 4 ) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^ In this study , we demonstrate that both TRAIL sensitive and TRAIL resistant breast cancer cell lines can be efficiently killed by overexpression of the TRAIL receptor , death receptor 4 ( DR 4 ) . ^^^ Death receptor 4 ( DR 4 ) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^ When driven by the strong CMV promoter , expression of DR 4 killed over 90 % of cells in five out of six cell lines tested in the absence of exogenous TRAIL . ^^^ When driven by the relatively weak tumor specific hTERT promoter , DR 4 was less effective alone , but sensitized cells to killing by TRAIL . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Therefore , we investigated the effect of H . pylori on the expression of TRAIL , FasL and their receptors ( TRAIL R 1 R4 , Fas ) in gastric epithelial cells and examined their role in apoptosis . ^^^ In addition , H . pylori caused a selective up regulation of TRAIL , TRAIL R 1 and Fas mRNA and protein expression in gastric cancer cells . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
These glioblastoma cell lines expressed TRAIL R 2 , but not TRAIL R 1 , R 3 , or R 4 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Virus mutants containing deletions that span E 3 were used to show that the RID and E 3 6 . 7K proteins are both necessary for the internalization and degradation of TR 2 , whereas only the RID protein is required for TRAIL receptor 1 downregulation . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
In this study , we searched for murine analogues of the four death receptor types ( TRAIL R 1 to R 4 ) , targeted by the tumour necrosis factor related apoptosis inducing ligand ( TRAIL ) , which were recently identified in the human brain . ^^^ Antisera against human TRAIL R 1 , TRAIL R 3 and TRAIL R 4 failed to reveal any other murine TRAIL receptor analogue . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Sensitization of multidrug resistant human ostesarcoma cells to Apo 2 Ligand / TRAIL induced apoptosis by inhibition of the Akt / PKB kinase . ^^^ 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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
These findings suggest that DR 4 aggregation mediated by camptothecin or VP 16 could represent a mean that accelerates TRAIL induced apoptosis . . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Increased TRAIL sensitivity during colorectal carcinogenesis has been previously attributed to changes in the balance between TRAIL receptors TRAIL R 1 and R 2 and `` decoy ' ' receptors TRAIL R 3 and R 4 during malignant progression . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
RESULTS : In patients infected with cagA+ / vacAs1+ H . pylori strains , expression of TRAIL and the proapoptotic receptors TRAIL R 1 and R 2 was down regulated , whereas expression of the antiapoptotic receptors TRAIL R 3 and R 4 was up regulated . ^^^ Furthermore , expression of TRAIL and TRAIL R 1 and R 2 correlated inversely with the severity of gastric inflammation . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
For example , in Ad / E3 infected cells , surface expression of MHC 1 was down regulated , as was cell surface display of death receptors Fas and TRAIL Receptor 1 . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
Investigation into the mechanism responsible for increased TRAIL responsiveness revealed increased levels of TRAIL R 1 and R 2 in membrane lipid rafts following depsipeptide treatment . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
TRAIL and its receptors TRAIL R 1 and TRAIL R 4 were constitutively expressed in normal epidermis and not altered in a variety of inflammatory dermatoses including those associated with interface dermatitis . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ 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 . ^^^ Taken together , gene mutations of TRAIL R 1 , TRAIL R 2 are infrequent in patients with CML and MDS . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
On the other hand , `` death receptor ' ' TRAIL R 1 , `` decoy receptors ' ' TRAIL R 3 , and TRAIL R 4 were barely detectable or undetectable at any time point examined . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ Here , we describe the characterisation and activity of HGS ETR 1 , the first fully human , agonistic TRAIL R 1 mAb that is being developed as an antitumour therapeutic agent . ^^^ HGS ETR 1 showed specific binding to TRAIL R 1 receptor . ^^^ HGS ETR 1 reduced the viability of multiple types of tumour cells in vitro , and induced activation of caspase 8 , Bid , caspase 9 , caspase 3 , and cleavage of PARP , indicating activation of TRAIL R 1 alone was sufficient to induce both extrinsic and intrinsic apoptotic pathways . ^^^ HGS ETR 1 , a fully human TRAIL receptor 1 monoclonal antibody , induces cell death in multiple tumour types in vitro and in vivo . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Of note , in a subset of B CLL samples , the addition to B CLL cultures of a TRAIL R 1 Fc chimera , which binds at high affinity to surface TRAIL , significantly decreased the percentage of viable cells with respect to untreated control B CLL cells , suggesting that surface TRAIL may play an unexpected role in promoting B CLL cell survival . ^^^ 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 O00220	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 . ^^^ In addition , matched tumor and peripheral blood DNA samples were screened for 2 known TRAIL R 1 coding single nucleotide polymorphisms ( C626G and G422A ) . ^^^ 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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
The expression of TRAIL , TRAIL R ( DR 4 , DcR 1 ) and Fas L in patients with ovarian cancer ] . ^^^ OBJECTIVE : To investigate the apoptosis induced by TRAIL , TRAIL R and Fas L in patients METHODS : The expression of TRAIL , TRAIL R ( DR 4 , DcR 1 ) and Fas L in ovarian cancer was detected with immunohistochemistry . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Chronic lymphocytic leukemic cells exhibit apoptotic signaling via TRAIL R 1 . ^^^ The apoptosis inducing ability of these mAbs and different TRAIL preparations , in the presence or absence of histone deacetylase inhibitors ( HDACi ) , varied markedly against primary chronic lymphocytic leukaemia ( CLL ) cells and various tumor cell lines , demonstrating an unanticipated preferential apoptotic signaling via either TRAIL R 1 or R 2 . ^^^ 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 . ^^^ Thus combination of an agonistic TRAIL R 1 Ab and an HDACi , such as the anticonvulsant sodium valproate , could be of value in treating CLL . . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Lack of expression of TRAIL receptor 1 ( death receptor 4 , DR 4 ) correlates with resistance to TRAIL induced apoptosis in ovarian cancer cells . ^^^ Contribution of epigenetic silencing of tumor necrosis factor related apoptosis inducing ligand receptor 1 ( DR 4 ) to TRAIL resistance and ovarian cancer . ^^^ Reconstitution of DR 4 in the TRAIL resistant A 2780 ovarian cancer cell line was investigated with the demethylating agent 5 aza 2 ' deoxycytidine and transient gene transfer . ^^^ Regulation of DR 4 expression by demethylation or transient transfection is of functional relevance for TRAIL resistance in an ovarian cancer cell line . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
DMSO sensitized cells towards induction of apoptosis by anti Fas antibody , tumour necrosis factor alpha or Apo 2 ligand / TNF related apoptosis inducing ligand ( TRAIL ) . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
The combination of triterpenoids and monoclonal anti TRAIL receptor 1 ( DR 4 ) antibody also induces apoptosis of breast cancer cells in vitro . ^^^ 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 O00220	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 . ^^^ We show that HER2 / PI3K / Akt pathway may play a specific pro apoptotic role in certain cell type by inducing TRAIL R 1 and R 2 expression and thereby enhancing responsiveness to TRAIL . . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 . ^^^ RESULTS : TRAIL R 1 expression was not associated with survival . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
A single nucleotide polymorphism in the extracellular domain of TRAIL receptor DR 4 at nucleotide 626 in gastric cancer patients in Japan . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ In vitro studies showed that TRAIL induced apoptosis was dependent on TRAIL R 1 and / or R 2 dosage in most tumors . ^^^ 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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
The enhanced NFkappaB activity resulted in the elevation of TRAIL and its receptor DR 4 , both known to induce apoptosis . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL induced human oligodendrocyte ( hOL ) death depends on TRAIL ligation with its receptor 1 ( TRAIL R 1 ) . ^^^ However , the intracellular signaling initiated with ligation of TRAIL R 1 in hOLs is unknown . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ Ala 228 variant of trail receptor 1 affecting the ligand binding site is associated with chronic lymphocytic leukemia , mantle cell lymphoma , prostate cancer , head and neck squamous cell carcinoma and bladder cancer . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ Recent observations suggesting that DR 4 is the predominant receptor for the cytotoxic effects of TRAIL in CLL and that histone deacetylase inhibitors synergize with TRAIL in CLL in vitro are described and discussed . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
The expression of surface TRAIL and TRAIL R 1 , R 2 , R 3 , R 4 were examined by flow cytometry in the immortalized human cell line tsFHI under culture conditions promoting growth or growth arrest and expression of differentiated traits . ^^^ In spite of the presence of TRAIL R 1 and TRAIL R 2 `` death receptors , ' ' recombinant TRAIL was not cytotoxic for tsFHI cells . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
High sensitivity to TRAIL induced apoptosis was characteristic for DR 4 positive melanoma cells , whereas DR 4 negative cells showed less and delayed response or were resistant . ^^^ Thus , DR 4 expression in vivo and the high efficiency of DR 4 mediated apoptosis may suggest reassessment of the suitability of TRAIL and especially of DR 4 based strategies for melanoma treatment . . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL receptor selective mutants signal to apoptosis via TRAIL R 1 in primary lymphoid malignancies . ^^^ 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 . ^^^ Based on studies using agonistic monoclonal antibodies , we recently proposed that primary chronic lymphocytic leukemic cells seem to signal apoptosis primarily through TRAIL R 1 . ^^^ We have now synthesized mutant forms of TRAIL specific for TRAIL R 1 or TRAIL R 2 . ^^^ Using these mutants , we now unequivocally show that primary cells from patients with chronic lymphocytic leukemia and mantle cell lymphoma signal to apoptosis almost exclusively through TRAIL R 1 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Inhibition of methyltransferases by decitabine resulted in considerable up regulation of TRAIL receptor 1 and caspase 8 , down regulation of PED / PEA 15 , inhibition of cell growth , and sensitization of primary glioblastoma cells to TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	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 O00220	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 ) . ^^^ Multivariate analysis of TRAIL R 1 within the study group ( n=62 ) showed that age , gender , staining intensity , antigenic load , % of TRAIL R 1 expression , were not statistically correlated with survival however radiotherapy was significantly correlated ( multivariate analysis : age : P=0 . 15 ; gender : P=0 . 64 ; staining intensity : P=0 . 17 ; antigenic load : P=0 . 056 ; % of TRAIL R 1 expression : P=0 . 058 ; radiotherapy : P=0 . 0001 ) . ^^^ Subgroup analysis of patients who had received radiotherapy ( n=47 ) showed a significant association of % of TRAIL R 1 expression and the antigenic load of TRAIL R 1 with survival ( multivariate analysis : P=0 . 036 , respectively , P=0 . 023 ) . ^^^ RT PCR analysis detected a negative relation between the amount of TRAIL R 1 mRNA and the WHO grade of astrocytic tumors ( P=0 . 03 ) . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	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 O00220	Pubmed	SVM Score :0.0
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 O00220	Pubmed	SVM Score :0.0
Topotecan and gimatecan induced moderate up regulation of TRAIL R 1 and R 2 which resulted in a different cell response to the combination in androgen independent cells ( DU 145 and PC 3 ) . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
TRAIL is a member of the tumor necrosis factor superfamily that interacts with an unusually complex receptor system , comprising transmembrane ( TRAIL R 1 , R 2 , R 3 and R 4 ) and soluble ( osteoprotegerin ) receptors . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
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 O00220	Pubmed	SVM Score :0.0
The synergism seemed to rely partly on the enhanced expression of TRAIL receptor 1 ( TRAIL R 1 ; DR 4 ) , analyzed by immunofluorescence , by 1 methoxy canthin 6 one . ^^^ Cell incubation with 1 methoxy canthin 6 one resulted in activating c Jun NH 2 terminal kinase ( JNK ) , as revealed by Western blotting ; induction of apoptosis and TRAIL R 1 up regulation by 1 methoxy canthin 6 one were > 80 % prevented by the addition of the JNK inhibitor ( JNKI ) SP600125JNKI , indicating that both effects were almost completely mediated by JNK activity . ^^^ On the other hand , synergism with TRAIL was reduced by about 50 % , suggesting that besides up regulating TRAIL R 1 , 1 methoxy canthin 6 one could influence other factor ( s ) that participated in TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 O00220	Pubmed	SVM Score :0.0
This reduction in apoptosis in Adeno infected epithelial cells by corticosteroids exposure induced a prolonged virus production via both DR 4 and TRAIL protein suppression . ^^^ This results from decreased DR 4 and TRAIL expression . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^ TRAIL R 1 expression was not associated with survival . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Based on these data and our previous studies , we propose that a clinical trial in CLL is warranted using a combination of a selective HDACi that inhibits HDAC 1 and / or HDAC 2 together with a form of TRAIL that signals through TRAIL receptor 1 . . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Nitrosylcobalamin promotes cell death via S nitrosylation of Apo2L / TRAIL receptor DR 4 . ^^^ Furthermore , the Apo2L / TRAIL death receptor DR 4 ( TRAIL R 1 ) was S nitrosylated following NO Cbl treatment . ^^^ Cells expressing the DR 4 C336A mutant were more resistant to NO Cbl and Apo2L / TRAIL than were the other six C A mutations or wild type cells . ^^^
Interacting proteins: P50591 and O00220	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 . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
Compared with a sensitive cell line ( early passage NB 16 ) , the resistant cell lines ( NB 7 and late passage NB 16 ) expressed lesser amounts of the death inducing TRAIL R 1 and R 2 , and greater levels of survivin , an inhibitor of apoptosis . ^^^
Interacting proteins: P50591 and O00220	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 O00220	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 O00220	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 % ) . ^^^
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and O00220	Pubmed	SVM Score :0.0
NA