Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.77263682
Indeed , we found that treatment of Jurkat cells with 3 , 4 , 5 THS , unlike treatment with resveratrol , induced activation of caspase 8 and apoptosis by a Fas associated death domain ( FADD ) protein dependent mechanism without involving the known death ligands CD 95 ligand ( CD95L ) , tumor necrosis factor alpha ( TNFalpha ) and TNF related apoptosis inducing ligand ( TRAIL ) . 0.77263682^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The caspase inhibitors , zIETD fmk and zDEVD fmk , inhibited apoptosis in AIDS KS by sApo 2L , suggesting that caspase 3 like and caspase 8 or 10 activities are essential for Apo 2L mediated apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Apo 2L induced apoptosis was associated with the processing of caspase 8 , Bid , and the cytosolic accumulation of cytochrome c as well as the processing of caspase 9 and caspase 3 . ^^^ Cotreatment with either a caspase 8 or a caspase 9 inhibitor suppressed Apo 2L induced apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Gel shift assay and Western blot analysis supported microarray results , showing that 5 PYRRO / NO suppressed GlaN / LPS induced activation of nuclear factor kappaB and GlaN / LPS induced increases in caspase 1 , caspase 8 , tumor necrosis factor receptor 1 ( TNFR 1 ) associated death domain , and TNF related apoptosis inducing ligand . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In this study , TNF alpha alone induced NF kappaB nuclear translocation , cIAP 1 and cIAP 2 up regulation , and MM cell proliferation ; in contrast , SN 50 pretreatment sensitized MM cells to TNF alpha induced apoptosis and cleavage of caspase 8 and caspase 3 , similar to our previous finding of SN 50 induced sensitization to apoptosis induced by the TNF alpha family member TNF related apoptosis inducing ligand ( TRAIL ) / Apo2L . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We have previously reported that TNF related apoptosis inducing ligand ( TRAIL ) causes cleavage of Bid via activation of caspase 8 and the loss of mitochondrial membrane potential ( DeltaPsim ) , resulting in apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Because cellular FLICE / caspase 8 inhibitory protein ( cFLIP ) is a recently identified intracellular inhibitor of caspase 8 activation that potently inhibits death signaling mediated by all known death receptors , including Fas , TNF receptor ( TNF R ) , and TNF related apoptosis inducing ligand receptors ( TRAIL Rs ) , we investigated the expression and function of cFLIP in human HCCs . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Fanconi anemia type C deficient hematopoietic cells are resistant to TRAIL ( TNF related apoptosis inducing ligand ) induced cleavage of pro caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In this study , to specify caspase 8 mediated apoptotic activity , we examined the anti tumor effect of adenoviral vector expressing caspase 8 ( Adv caspase 8 ) in combination with TNF related apoptosis inducing ligand ( TRAIL ) which induces specifically caspase 8 activation . ^^^
Interacting proteins: P50591 and Q14790	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 Q14790	Pubmed	SVM Score :0.0
Since caspase 8 activation is associated with the activation of death receptors , such as Fas , tumor necrosis factor ( TNF ) , or TNF related apoptosis inducing ligand ( TRAIL ) receptors , studies were conducted to determine the exact death receptor ( s ) and ligand ( s ) involved in mediating tocotrienol induced caspase 8 activation and apoptosis . ^^^
Interacting proteins: P50591 and Q14790	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 Q14790	Pubmed	SVM Score :0.0
Consequently , activation of caspase 8 and downstream caspases upon addition of TNF related apoptosis inducing ligand ( TRAIL ) was restored by pretreatment with 5 dAzaC and IFN gamma . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Exogenous Apo2L induced phosphatidylserine exposure on cell membranes , caspase 8 and caspase 3 activation , key markers of apoptosis , confirming that the Apo2L / DR5 pathway is functional in these cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Another death domain containing receptor for TRAIL ( designated as death receptor 5 ) , which preferentially engaged a FLICE ( caspase 8 ) related death protease , was also identified . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In these cells , TRAIL induced cell death and activation of the apoptosis executioner caspase 8 ( FLICE / MACH ) and caspase 3 ( YAMA , CPP 32 , Apopain ) , that belong to caspase subfamily of cysteine proteases , were abrogated , whereas JNK activation remained unaffected and was still sensitive toward z VAD fmk . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL causes cleavage of bid by caspase 8 and loss of mitochondrial membrane potential resulting in apoptosis in BJAB cells . ^^^ SDS PAGE and Western blot analysis showed that cleavage of Bid was induced by a 1 h incubation of BJAB cells with TRAIL and was blocked by a caspase 8 inhibitor . ^^^ The time course study suggests that TRAIL causes cleavage of Bid via activation of caspase 8 , subsequently the loss of mitochondrial membrane potential , resulting in apoptosis in BJAB cells . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
This sensitization concomitantly resulted in processing of caspase 8 , which did not occur in TRAIL resistant PK . ^^^ Interestingly , cellular FLICE inhibitory protein ( cFLIP ) levels , high in PK and low in TK and several other squamous cell carcinoma cell lines , decreased rapidly after treatment of PK with CHX , correlating with the increase in TRAIL sensitivity and caspase 8 processing . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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 Q14790	Pubmed	SVM Score :0.0
Cleavage of caspase 8 and its preferred substrate , Bid , preceded processing of caspases 7 and 9 , indicating that caspase 8 is the apical initiator caspase in TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In addition Mad 1 interfered with Fas , TRAIL , and UV induced apoptosis , which coincided with a reduced activation of caspase 8 during Fas mediated apoptosis in response to Mad 1 expression . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL receptor 2 signals apoptosis through FADD and caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Inhibition of caspases prevented TRAIL / anti APO 1 induced apoptosis , but not NF kappaB activation , indicating that both pathways bifurcate upstream of the receptor proximal caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In addition , caspase 8 deficient cells are resistant against TRAIL induced apoptosis , and inhibition of caspase 8 but not caspase 9 prevents mitochondrial permeability transition and apoptosis . ^^^ This indicates that TRAIL induced apoptosis depends on caspase 8 activation rather than on the disruption of mitochondrial integrity . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
One medullary carcinoma cell line was resistant to Fas and TRAIL induced apoptosis , even in the presence of cycloheximide , and to transfection of constitutively active caspase 8 , suggesting a different regulation of the apoptotic pathway . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL induced death signal was inhibited with both decreased caspase 8 and caspase 3 activity . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Whereas both S and N type cell lines express TRAIL R 2 , FADD , and caspase 3 and 10 , only S type cells express caspase 8 . ^^^ Caspase 8 expression can be induced by demethylation with 5 aza 2 ' deoxycytidine , which enhances sensitivity to TRAIL . ^^^ Therefore , caspase 8 expression is silenced in malignant NB , which correlates to tumor severity and resistance to TRAIL induced apoptosis . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The apoptotic programme in the sensitive ESFT VH 64 cell line revealed TRAIL induced activation of FLICE / MACH1 ( caspase 8 ) and CPP32 / Yama / apopain ( caspase 3 ) and processing of the prototype caspase substrate poly ( ADP ribose ) polymerase . ^^^ Inhibition of caspase 8 and caspase 3 by zIETDfmk and zDEVDfmk , respectively , substantially prevented TRAIL induced apoptosis . ^^^ However , zIETDfmk , but not zDEVDfmk , reduced TRAIL mediated DeltaPsi ( m ) dissipation , indicating that TRAIL causes mitochondrial dysfunction through caspase 8 acting upstream of mitochondria . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
To detect the expression of apoptosis related molecules , ribonuclease protection assay was used with specific antisense RNA probes for Fas , Fas ligand , TNFR 1 , TRAIL , FADD , TRADD , RIP , FAF , FAP , and caspase 8 . ^^^ Immunostaining for Fas , Fas ligand , TRAIL , TRADD , RIP , and caspase 8 was also performed . ^^^ Compared with control and contralateral kidneys , the ligated kidneys displayed a dynamic expression of mRNAs for many apoptosis related molecules , which included an up to threefold increase for Fas , Fas ligand , TNF R 1 , TRAIL , TRADD , RIP , and caspase 8 , and an up to twofold increase for FADD and FAP , but there was little change for FAF . ^^^ Although increased expression of TRAIL , TRADD , RIP , and caspase 8 was noted in tubular cells , there was no staining for these molecules in interstitial cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
FADD / MORT1 and caspase 8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2 . ^^^ Analysis of the native TRAIL death inducing signaling complex ( DISC ) revealed ligand dependent recruitment of FADD / MORT1 and caspase 8 . ^^^ Differential precipitation of ligand stimulated TRAIL receptors demonstrated that FADD / MORT1 and caspase 8 were recruited to TRAIL R 1 and TRAIL R 2 independently of each other . ^^^ FADD / MORT1 and caspase 8 deficient Jurkat cells expressing only TRAIL R 2 were resistant to TRAIL induced apoptosis . ^^^ Thus , FADD / MORT1 and caspase 8 are essential for apoptosis induction via TRAIL R2 . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Thus , Fas , TRAIL and TNF receptors can initiate cell death by two alternative pathways , one relying on caspase 8 and the other dependent on the kinase RIP . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Both HCT 116 and SW 480 cells were protected from TRAIL by the caspase 8 inhibitor Z IETD FMK , dominant negative FADD and cellular FLIP s and interestingly both cell lines displayed caspase 9 cleavage to a similar extent after TRAIL exposure . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Resistance to TRAIL induced apoptosis in neuroblastoma cells correlates with a loss of caspase 8 expression . ^^^ CONCLUSIONS : Treatment with 5 aza 2 ' deoxycytidine restored mRNA expression of caspase 8 and 10 and TRAIL sensitivity of resistant cell lines , suggesting that gene methylation is involved in caspase inactivation . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Resistance to TRAIL induced apoptosis in primitive neuroectodermal brain tumor cells correlates with a loss of caspase 8 expression . ^^^ 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 . ^^^ However , all TRAIL sensitive PNET cell lines expressed caspase 8 mRNA and protein , while none of the five TRAIL resistant PNET cell lines expressed caspase 8 protein . ^^^ Treatment with the methyltransferase inhibitor 5 aza 2 ' deoxycytidine restored mRNA expression of caspase 8 and TRAIL sensitivity in formerly TRAIL resistant PNET cells , suggesting that gene methylation inhibits caspase 8 transcription in these cells . ^^^ We conclude , that loss of caspase 8 mRNA is an important mechanism of TRAIL resistance in PNET cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Reconstitution of caspase 8 sensitizes JB 6 cells to TRAIL . ^^^ We report here that caspase 8 is required in TRAIL induced cell death . ^^^ Acetyl IETD fluoromethylketone , a caspase 8 inhibitor , potently suppressed TRAIL induced cell death compared to acetyl DEVD fluoromethylketone and acetyl LEHD fluoromethylketone , inhibitors of caspase 3 and caspase 9 , respectively . ^^^ JB 6 cells , a caspase 8 deficient Jurkat variant , were completely resistant to TRAIL . ^^^ However , reconstitution with a caspase 8 , but not with caspase 2 or 3 , sensitized JB 6 cells to subsequent exposure to TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The TRAIL DISCussion : It is FADD and caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Data suggest that caspase 8 may be sufficient to deliver the TRAIL induced apoptotic signal in the absence of both caspase 10 and c FLIP ( Rh 18 ) but not in the presence of c FLIP ( Rh 41 ) . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Taken together , these results suggest that TRAIL induces apoptosis of melanoma cells by recruitment of mitochondrial pathways to apoptosis that are dependent on activation of caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Treatment of LNCaP cells with TRAIL alone induced cleavage of the caspase 8 and XIAP proteins . ^^^ Blocking cytochrome c release by Bcl 2 overexpression rendered LNCaP cells resistant to TRAIL plus wortmannin treatment but did not affect caspase 8 or BID processing . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Loss of function KILLER / DR5 mutants were deficient in recruitment of FADD and caspase 8 to TRAIL death inducing signaling complexes . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In addition , expression of Toso , a cell surface apoptosis regulator , seemed to block activation of caspase 8 by TRAIL via enhanced expression of FLIPL in granulocytic differentiated cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Loss of caspase 8 expression in neuroblastoma is related to malignancy and resistance to TRAIL induced apoptosis . ^^^ RESULTS : Although both S and N type cell lines express TRAIL R 2 , FADD , and caspases 3 and 10 , only S type cells express caspase 8 . ^^^ CONCLUSIONS : Therefore , caspase 8 expression is silenced in malignant NB , which correlates to tumor severity and resistance to TRAIL induced apoptosis . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In Colo 357 cells retrovirally transduced with Bcl XL , caspase 8 activation in response to treatment with TRAIL or anti CD 95 antibody was not different from parental cells and EGFP transfected controls , however , apoptosis was completely suppressed as measured by the mitochondrial transmembrane potential deltapsim , caspase 3 activity ( PARP cleavage ) and DNA fragmentation . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL has no effect on Delta psi ( m ) and apoptosis in Jurkat cells deficient in either FADD or caspase 8 , suggesting both FADD and caspase 8 are required for TRAIL signaling . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The CD 437 and TRAIL combination enhanced activation of caspase 3 , caspase 7 , caspase 8 , and caspase 9 and the subsequent cleavage of poly ( ADP ribose ) polymerase and DNA fragmentation factor 45 . ^^^ These results suggest that the mechanism of enhanced apoptosis by this combination involves p 53 dependent increase of death receptors by CD 437 , activation of these receptors by TRAIL , enhanced Bid cleavage , release of cytochrome c , and activation of caspase 3 , caspase 7 , caspase 8 , and caspase 9 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Sensitivity to TRAIL stimulated apoptosis did not correlate with expression of death receptors , decoy receptors , or expression of the caspase 8 inhibitory protein cFLIP . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The combination of actinomycin D and TRAIL induced an almost complete lysis of Aspc 1 cells , whereas actinomycin D alone had no effect on cell survival but inhibited the expression of the Flice inhibitory protein , which is assumed to play a role in the apoptotic pathway of TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Apoptosis induced by combined treatment of TRAIL and radiation in TRAIL resistant cells was associated with cleavage of caspase 8 and the proapoptotic Bid protein , resulting in the activation of caspase 9 and caspase 3 . ^^^ These results demonstrated that ionizing radiation in combination with TRAIL could overcome resistance to TRAIL in TRAIL resistant cells through TRAIL receptor independent synergistic activation of the cascades of the caspase 8 pathway , suggesting a potential clinical application of combination treatment of TRAIL and ionizing radiation to TRAIL resistant cancer cells . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The involvement of the TRAIL pathway was further confirmed by the activation of caspase 8 in Mifepristone treated cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Nine of 10 ESFT cell lines , including several that were Fas resistant , underwent apoptosis with TRAIL through activation of caspase 10 , capase 8 ( FLICE ) , caspase 3 , and caspase 9 . ^^^ Levels of DcR 1 and DcR 2 or levels of the FLICE inhibitory protein ( FLIP ) did not correlate with TRAIL resistance , and protein synthesis inhibition did not sensitize the TRAIL resistant line to TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Fas associated death domain protein ( FADD ) and caspase 8 mediate up regulation of c Fos by Fas ligand and tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) via a FLICE inhibitory protein ( FLIP ) regulated pathway . ^^^ FasL and TRAIL mediated up regulation of c Fos was completely dependent on the presence of Fas associated death domain protein ( FADD ) and caspase 8 , but caspase activity seemed to be dispensable as a pan inhibitor of caspases had no inhibitory effect . ^^^ Upon overexpression of the long splice form of cellular FADD like interleukin 1 converting enzyme ( FLICE ) inhibitory protein ( cFLIP ) in Jurkat cells , FasL and TRAIL induced up regulation of c Fos was almost completely blocked . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
BeAn infection of activated cells resulted in increased caspase 8 mRNA transcripts and the appearance of TNF alpha related apoptosis inducing ligand ( TRAIL ) 4 h postinfection . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Examination of the TRAIL DISC in sensitive and resistant cells suggests that a high ratio of c FLIP to caspase 8 may partially explain cellular resistance to TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
FLIP ( FLICE Inhibitory Protein ) is a recently identified intracellular inhibitor of caspase 8 activation that potently inhibits cell death mediated by all death receptors including Fas and TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The activation of a self amplifying cascade of caspases , of which caspase 8 is the apical protease , mediates Fas , tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) , and TNF alpha induced apoptosis in colon cell lines . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Lastly , TRAIL / Apo2L induced apoptosis in MM cells was dependent on caspase 8 activation and inhibited by the caspase regulatory proteins FLIP and cIAP 2 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Bax deficiency has no effect on TRAIL induced caspase 8 activation and subsequent cleavage of Bid ; however , it results in an incomplete caspase 3 processing because of inhibition by XIAP . ^^^ Release of Smac / DIABLO from mitochondria through the TRAIL caspase 8 tBid Bax cascade is required to remove the inhibitory effect of XIAP and allow apoptosis to proceed . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 and caspase 3 and poly ( ADP ribose ) polymerase cleavage was activated within 2 hours after stimulation with 200 ng / mL TRAIL . ^^^ CONCLUSION : These findings suggest a relation between osteoprotegerin expression and the biologic aggressiveness of PDC and the involvement of caspase 8 and caspase 3 activation in the TRAIL mediated apoptosis pathway in PDC . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Our findings indicate that FADD and Caspase 8 are essential for FasL and TRAIL mediated apoptosis in glioma cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In tumor cell lines resistant to TRAIL , anti CD 95 or TNFalpha , caspase 8 protein and mRNA expression was decreased or absent without caspase 8 gene loss . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We have examined caspase 8 activity , BID cleavage , Akt activity , mitochondrial membrane potential ( DeltaPsi ( m ) ) and apoptosis in prostate cancer ( LNCap , PC 3 , PC 3M and DU 145 ) cells treated with or without TRAIL . ^^^ TRAIL activates caspase 8 in all the cell lines . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The ability of interferon gamma when combined with TNF alpha to mediate keratinocyte apoptosis included induction of TRAIL coupled with diminished capacity of keratinocytes with repressed NF kappaB activity to increase the TRAIL decoy receptor 1 , as well as lower levels of several NF kappaB dependent antiapoptotic proteins accompanied by enhanced caspase 8 levels . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 dependent sensitization of cancer cells to TRAIL induced apoptosis following reovirus infection . ^^^ Sensitization is associated with an increase in the activity of the death receptor associated initiator caspase , caspase 8 , and is inhibited by the peptide IETD fmk , suggesting that reovirus sensitizes cancer cells to TRAIL induced apoptosis in a caspase 8 dependent manner . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Enhancement of Apo2L / TRAIL ( tumor necrosis factor related apoptosis inducing ligand ) induced apoptosis in non small cell lung cancer cell lines by chemotherapeutic agents without correlation to the expression level of cellular protease caspase 8 inhibitory protein . ^^^ In addition , endogenous expression levels of the caspase inhibiting cellular protease caspase 8 inhibitory protein ( C FLIP ) were measured to investigate partial resistance to Apo2L / TRAIL . ^^^ Western blot analysis showed that sensitization to Apo2L / TRAIL did not correlate with the expression of cellular protease caspase 8 inhibitory protein . ^^^ Resistance and sensitization to Apo2L / TRAIL are not correlated with the endogenous expression level of cellular protease caspase 8 inhibitory protein , implying that in non small cell lung cancer other mechanisms are responsible for inhibition of the Apo2L / TRAIL pathway . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
However , the combination of TRAIL ( 50 ng / ml ) and glucose deprivation for 4 h increased cell death and PARP cleavage by promoting activation of caspase 8 and caspase 3 , relative to that of TRAIL alone . ^^^ Data from immunoblotting analysis reveal that glucose deprivation enhanced TRAIL cytotoxicity is inversely related to the intracellular level of FLICE inhibitory protein ( FLIP ) but not that of death receptor 5 ( DR 5 ) . ^^^
Interacting proteins: P50591 and Q14790	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 . ^^^ In primitive neuroectodermal brain tumour ( PNET ) cell lines , TRAIL induced apoptosis was recently shown to correlate with caspase 8 mRNA expression ( Grotzer MA , Eggert A , Zuzak TJ , et al . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The evidence that Fas L ( + ) / TRAIL ( + ) malignant plasma cells prime erythroblast apoptosis by direct cytotoxicity was also supported by the increase of FLICE in fresh immature GpA ( +dim ) erythroid cells , whereas ICE and caspase 10 increased in subsequent maturative forms . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Indeed , in 293 , HeLa and Jurkat cells , cell death mediated by agonistic anti Fas antibody , TRAIL or overexpression of full length caspase 8 was significantly inhibited by overexpression of PDCasp 8 or PDCasp 10 which colocalized with the Golgi complex and with overexpressed FADD . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL mediated apoptosis involved cleavage of Bid , caspase 3 , and PARP , and required caspase 8 and 9 activity . ^^^
Interacting proteins: P50591 and Q14790	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 Q14790	Pubmed	SVM Score :0.0
Up regulation of caspase 8 expression and activation were detected as a result of pretreatment with IFN gamma and subsequent apoptosis mediated by TRAIL . ^^^ CONCLUSION : Our results demonstrated that IFN gamma sensitises human colon carcinoma cells to TRAIL mediated apoptosis , partly by elevated caspase 8 expression . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Bcl 2 overexpression reduced TRAIL induced cleavage of caspase 8 and Bid indicating that caspase 8 was activated upstream and also downstream of mitochondria in a feedback amplification loop . ^^^ In contrast , in SKW lymphoblastoid cells , TRAIL induced activation of caspase 8 directly translated into full activation of caspases , cleavage of XIAP , DFF 45 or PARP and apoptosis independent of Bcl 2 overexpression , although Bcl 2 similarly inhibited loss of mitochondrial membrane potential and the release of cytochrome c , AIF and Smac from mitochondria in all cell types . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Moreover , ectopic expression of IRF 1 induced caspase 8 expression thereby sensitizing cells for TRAIL , APO 1 or doxorubicin induced apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We found that TG upregulation of DR 5 and TRAIL was coupled with caspase 8 activation and Bid cleavage , suggesting that the TG regulated DR 5 pathway could be linked to the mitochondrial pathway . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 and caspase 10 were recruited to the DISC , where they were proteolytically activated to initiate apoptosis in TRAIL sensitive glioma cells . ^^^ Caspase 8 and caspase 10 were also recruited to the DISC in TRAIL resistant cells , but their further activation was inhibited by two antiapoptotic proteins termed cellular Fas associated death domain like interleukin 1beta converting enzyme inhibitory protein ( c FLIP ) and phosphoprotein enriched in diabetes / phosphoprotein enriched in astrocytes 15kDa ( PED / PEA 15 ) . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Similar to CD 95 ligand ( CD95L ) , TRAIL signaling requires ligand receptor interaction ; the downstream signaling molecules , such as Fas associated death domain and caspase 8 , also seem similar . ^^^ The decrease in MMP induced by both ligands was caspase 8 mediated ; no difference in caspase 8 activation by TRAIL and CD95L was found . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Treatment of HL 60 cells with TRAIL induced caspase 8 activation within 2 4 h , but no activation could be seen in Bcl 2 expressing or Bcl xL expressing cells . ^^^ Overall , these results indicate that TRAIL induced apoptosis involves activation of caspase 8 , caspase 7 , caspase 3 , and BID cleavage , and Bcl 2 and Bcl xL prevents TRAIL induced apoptosis by abrogating caspase activation and BID cleavage . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
IFN gamma promoted TRAIL mediated activation of caspase 8 , Bcl 2 interacting domain death agonist ( Bid ) degradation , Bcl 2 associated 10 protein ( Bax ) translocation to mitochondria , cytochrome c release to the cytosol and activation of caspase 9 in these cell lines . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL receptor and CD 95 signal to mitochondria via FADD , caspase 8 / 10 , Bid , and Bax but differentially regulate events downstream from truncated Bid . ^^^ We conclude that FADD , caspase 8 / 10 , and caspase cleaved Bid are required for TRAIL receptor and CD 95 signaling to mitochondria , whereas Bax is a common accessory . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 10 is recruited to and activated at the native TRAIL and CD 95 death inducing signalling complexes in a FADD dependent manner but can not functionally substitute caspase 8 . ^^^ The involvement of the death adaptor protein FADD and the apoptosis initiating caspase 8 in CD 95 and TRAIL death signalling has recently been demonstrated by the analysis of the native death inducing signalling complex ( DISC ) that forms upon ligand induced receptor cross linking . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Expression of FADD dominant negative in HEK 293 cells that prevents the recruitment of caspase 8 and RIP to TRAIL death receptors also eliminates this increase . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Mitogen activated protein kinase / extracellular signal regulated kinase signaling in activated T cells abrogates TRAIL induced apoptosis upstream of the mitochondrial amplification loop and caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 activation is necessary but not sufficient for tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) mediated apoptosis in the prostatic carcinoma cell line LNCaP . ^^^ RESULTS : LNCaP is resistant to TRAIL but TRAIL transiently induces DEVDase activity and activation of caspase 8 ; caspase 2 , 3 , 7 , and 9 were not activated . ^^^ CONCLUSIONS : These results suggest that caspase 8 activation is necessary but not sufficient for TRAIL mediated apoptosis and is presumably blocked downstream of caspase 8 by the PI3K / Akt pathway . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Blood and liver were analyzed for plasma aminotransferase activity , liver histology , liver apoptotic nuclei , mRNA of several cytokines ( tumor necrosis factor [ TNF ] alpha , interleukin [ IL ] 1beta , IL 6 , and IL 10 ) , apoptotic ligands ( TRAIL ) , cytokine receptors ( TNFRp 55 ) , pro and antiapoptotic regulators / adaptors ( Fas receptor , FasL , FADD , TRADD , RIP , Bak , Bax , Bcl 10 , Bcl 2 and Bcl w ) , and caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We found that addition of a protein kinase C ( PKC ) activator to MCF 7 cultures prevented TRAIL induced apoptosis , by inhibiting a step downstream of both caspase 8 activation and BID cleavage . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We found that the emergence of resistance to Apo2L / TRAIL , after prolonged incubation with this cytokine , was associated with increased levels of FLICE inhibitory protein ( FLIP ) , and was overcome by cycloheximide and bisindolylmaleimide , that specifically down regulated FLIP expression , as well as by transfection of a FLIP anti sense oligonucleotide . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We detected rapid cleavage of caspases 8 , 9 , 3 , and 6 , as well as the caspase substrates poly ( ADP ribose ) polymerase ( PARP ) and DNA fragmentation factor 45 ( DFF 45 ) , but not caspase 10 , upon TRAIL treatment in sensitive MM cells , pointing to caspase 8 as the apical caspase of TRAIL signaling in MM cells . ^^^ These phenomena were not observed or were significantly delayed in TRAIL resistant MM cells , suggesting that resistance may arise from inhibition at the level of caspase 8 activation . ^^^ Our data set a framework for the clinical use of approaches that sensitize MM cells to TRAIL by agents that inhibit FLIP and cIAP 2 expression or augment caspase 8 activity . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 and 10 activation , bid cleavage , cytosolic cytochrome c , and caspase 3 activation by TRAIL were all increased by the bile acid glycochenodeoxycholate ( GCDCA ) . ^^^ However , both caspase 8 and caspase 10 recruitment and processing within the TRAIL death inducing signaling complex ( DISC ) were greater in GCDCA treated cells whereas recruitment of cFLIP long and short was reduced . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL mediated apoptosis depended on FADD , caspase 8 and 3 as demonstrated by the ability of FADDdn , CrmA , and pharmacologic caspase inhibitors to prevent apoptosis . ^^^ Inhibition of NF kappaB unmasks a TRAIL induced apoptotic signaling cascade that involves FADD , caspase 8 , the MPT , and caspase 3 . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
FLICE like inhibitory protein ( FLIP ) , an inhibitor of caspase 8 , ( also known as FLICE ) is regulated by the transcription factor nuclear factor kappaB ( NF kappaB ) and can contribute to TRAIL resistance . ^^^ FLICE like inhibitory protein ( FLIP ) , an inhibitor of caspase 8 , ( also known as FLICE ) is regulated by the transcription factor nuclear factor kappaB ( NF kappaB ) and can contribute to TRAIL resistance . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Inhibition of TRAIL sensitivity occurs at the level of BID cleavage , as caspase 8 activity was not affected . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Betaine did not affect the TLCS induced membrane trafficking of CD 95 and tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) receptor 2 to the plasma membrane or the TLCS induced recruitment of Fas associated death domain ( FADD ) and caspase 8 to the CD 95 receptor . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Resistance to TRAIL was upstream of caspase 8 activation , as little or no caspase 8 was processed in TRAIL treated B CLL cells . ^^^ Low levels of a TRAIL death inducing signalling complex ( DISC ) were formed in these cells , accompanied by the recruitment of endogenous FADD , caspase 8 and c FLIP ( L ) but not c FLIP ( S ) . ^^^ Thus the resistance of B CLL cells to TRAIL may be due partly to low surface expression of the death receptors resulting in low levels of DISC formation and also to the high ratio of c FLIP ( L ) to caspase 8 within the DISC , which would prevent further activation of caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In accordance with the presumed function of FLIP as an inhibitor of death receptor induced caspase 8 activation , down regulation of FLIP by siRNAs enhanced TRAIL induced caspase 8 activation . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
This sensitization was not mediated at the receptor proximal level of TRAIL DISC formation or caspase 8 activation but further downstream . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
This study shows that 2ME2 uses the extrinsic pathway for induction of apoptosis . 2ME2 treatment results in up regulation of death receptor 5 ( DR 5 ) protein expression in vitro and in vivo and renders cells more sensitive to the cytotoxic activities of the DR 5 ligand tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . 2ME2 induced apoptosis requires caspase activation and kinetic studies show the sequential activation of caspase 8 , caspase 9 , and caspase 3 . ^^^
Interacting proteins: P50591 and Q14790	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 Q14790	Pubmed	SVM Score :0.0
Similarities between preparations included : an enhanced ability for both Apo2L / TRAIL preparations to kill a greater relative percentage of HaCaT cells compared with keratinocytes ; enhanced cytotoxicity towards keratinocytes that had their NF B activity inhibited ; a dependence of both Apo2L / TRAIL preparations on FADD and caspase activation ; triggering of the same caspase cascades including caspase 8 and 3 ; and an ability to induce apoptosis even when HaCaT cells and keratinocytes were transduced to overexpress either Bcl 2 or Bcl 10 ( L ) ( survival factors that reduce susceptibility to UV light induced apoptosis ) . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In two TRAIL resistant cell lines , DU 145 and LNCaP , treatment with TRAIL alone resulted in processing of c FLIP ( L ) and initiated abortive caspase 8 proteolysis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Fas associated death domain protein ( FADD ) and caspase 8 , components of death inducing signaling complex ( DISC ) , as well as FLIP ( FLICE [ Fas associating protein with death domain like interleukin 1 converting enzyme ] / caspase 8 inhibitory protein ) , a negative regulator of caspase 8 , were expressed ubiquitously in Ph 1 positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Stable overexpression of both c FLIP ( L ) and c FLIP ( S ) rescued the cells from TRAIL mediated apoptosis with isoform specific effects on DISC recruited caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL activated caspase 8 but not caspase 9 or 10 in HL 60 cells . ^^^ Higher levels of the FLICE inhibitory protein , cFLIP ( L ) , were observed in TRAIL resistant cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Induction of caspase 8 by interferon gamma renders some neuroblastoma ( NB ) cells sensitive to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) but reveals that a lack of membrane TR1 / TR2 also contributes to TRAIL resistance in NB . ^^^ The resistance of neuroblastoma ( NB ) cells to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induced apoptosis has been attributed to a lack of caspase 8 expression . ^^^ However , the IFN gamma restoration of caspase 8 in some NB cells revealed persistent TRAIL resistance in most NB cell lines examined . ^^^ Furthermore , we have found that we can improve TRAIL sensitivity in NB by reconstituting caspase 8 with IFN gamma and TR 2 with chemotherapeutic agents . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Potentiation of Fas and TRAIL mediated apoptosis by IFN gamma in A 549 lung epithelial cells : enhancement of caspase 8 expression through IFN response element . ^^^ Taken together , these findings suggest that IFN gamma potentiates Fas and TRAIL mediated apoptosis by increasing caspase 8 expression via an IFN gamma response element in A 549 cells . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL and wortmannin together accelerated processing of caspase 8 on the DISC and apparently the release of caspase 8 from the DISC into the cytoplasm . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Moreover , IFN alpha pretreatment clearly augmented TRAIL mediated caspase 8 activation in HuH 7 cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
However , SK BR 3 breast tumour cells exhibiting increased expression level of Bcl 10 ( L ) were resistant to TRAIL , though upon exposure to TRAIL , caspase 8 and Bid were activated . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Finally , we found that betaAP strongly activated caspase 8 , and the cell permeable , selective caspase 8 inhibitor z IETD FMK prevents both betaAP and TRAIL induced neurotoxicity . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 and 3 activities were increased by TRAIL treatment and apoptosis was largely blocked by caspase 8 and 3 inhibitors . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Finally , S . aureus infection of osteoblasts in the presence of anti TRAIL antibody demonstrates that TRAIL mediates caspase 8 activation and apoptosis of infected cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
After treatment with TRAIL , both TRAIL sensitive and partial resistant clones showed high levels of activation of caspase 3 , caspase 8 , RIP and PARP . ^^^ Our results showed that the expression levels of DR 5 , the activation levels of caspase 8 , 3 and RIP were critical factors in determining TRAIL sensitivities in Jurkat cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Under the same conditions , the intracellular domain of both CD 95 and TRAIL R 2 bound both FADD and caspase 8 . ^^^ Although caspase 8 and FADD are obligatory for TNF mediated apoptosis , they are not recruited to a TNF induced membrane bound receptor signaling complex as occurs during CD 95 or TRAIL signaling , but instead must be activated elsewhere within the cell . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Coincubation of TRAIL and doxorubicin led to the overexpression of TRAIL R 2 resulting in a synergistic effect of doxorubicin and TRAIL in TRAIL sensitive cell lines and in the overcoming of TRAIL resistance in all of the TRAIL resistant cell lines , except HTB 91 , which lacked caspase 8 expression . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The site in the apoptotic pathway acted on by U 0126 appeared to be downstream of caspase 8 and Bid but upstream of caspase 3 in that the levels of proteolytic cleavage of caspase 8 and Bid by TRAIL were similar in cells with or without exposure to U 0126 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Moreover , exposure to TRAIL and / or IR resulted in a marked activation of initiator caspase 8 , possibly augmented by the observed reduction of inhibitory c FLIP expression . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The ability of TRAIL and daunorubicin to induce super additive apoptosis correlated with the ability of these agents to activate caspase 8 and to augment cellular levels of the truncated pro apoptotic form of the BCL 2 family member BID . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The release of cytochrome c could not be blocked by inhibitors of caspases 3 , 8 and 9 indicating that BADGE acts upstream of caspases 3 and 9 and does not involve caspase 8 to release cytochrome c . ( 4 ) While the caspase independent apoptotic effect might be mediated by AIF , the sensitizing effect of BADGE against other apoptotic substances is most likely mediated by the 10 linked inhibitor of apoptosis inhibitor Smac / DIABLO . ( 5 ) Our data suggest that BADGE or BADGE derivatives could represent promising substances for the treatment of neoplasms improving the antitumoral activity of TRAIL . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In the same time frame , TRAIL started to activate caspase 8 and caspase 3 , and to induce apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
To define molecular requirements for ErPC induced apoptosis , activation of caspases 8 , 9 and 3 and cleavage of the caspase 3 substrates PARP and ICAD were tested in normal Jurkat T cells , Jurkat cells resistant to death receptor ( CD 95 or TNFalpha related apoptosis inducing ligand ( TRAIL ) induced apoptosis , Jurkat cells lacking caspase 8 or Fas associated death domain ( FADD ) Jurkat cells expressing a dominant negative caspase 9 or overexpressing Bcl 2 as well as BJAB B lymphoma cells expressing a dominant negative FADD ( FADD DN ) . ^^^ ErPC induced apoptosis was independent from CD 95 receptor signaling and FADD since CD 95 and TRAIL resistant , caspase 8 and FADD negative Jurkat cells , as well as BJAB cells expressing FADD DN were sensitive to ErPC induced apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
HMGB 1 is also able to protect mammalian cells against different death stimuli including ultraviolet radiation , CD 95 , TRAIL , Casp 8 , and Bax induced apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
A caspase 8 independent component in TRAIL / Apo 2L induced cell death in human rhabdomyosarcoma cells . ^^^ Data demonstrate that in RMS cells , the TRAIL signaling pathway circumvents caspase 8 activation of Bid upstream of the mitochondria and that TRAIL acts at the level of the mitochondria via a mechanism that may involve components of the sphingomyelin cycle . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Unlike other cancer cells , most neuroblastoma cell lines are resistant to TRAIL induced apoptosis and the resistance correlates with caspase 8 deficiency , which is attributed to the methylation of the gene . ^^^ Interferon ( IFN ) gamma induces caspase 8 expression in most neuroblastoma cell lines regardless of the methylation status but fails to sensitize most NB to TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Neuroblastomas are characterized by defects in tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induced apoptosis , especially down regulation and methylation of Caspase 8 ( CASP 8 ) . ^^^ Here we found that ectopic N myc expression induces TRAIL susceptibility , both by CASP 8 and CASP 9 mediated apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
When PS 341 is combined with TRAIL , the levels of activated caspase 8 and cleaved Bid are substantially increased . ^^^ Taken together , these findings indicate that PS 341 enhances TRAIL induced apoptosis by increasing the cleavage of caspase 8 , causing Bak dependent release of mitochondrial proapoptotic proteins . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We have also shown that TRAIL was able to induce caspase 8 cleavage in these cells , whereas pretreatment with IL 8 blocked this caspase cleavage . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The combination of TRAIL and cisplatin synergistically enhanced apoptotic death , caspase 8 and caspase 3 activation , as well as poly ( ADP ribose ) polymerase cleavage . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
CDDP down regulated c FLIP , tending to lower the activation threshold required for TRAIL induced caspase 8 activation . ^^^ The CDDP pretreated cells indeed demonstrated more increased TRAIL mediated caspase 8 activation , loss of mitochondrial membrane potential ( DeltaPsi ( m ) ) , and apoptosis than untreated cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We therefore examined tumor cell lines of leukemic and nonleukemic origin with apoptosis resistance towards TRAIL because of absent Caspase 8 or dysfunctional FADD . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
RESULTS : The relative ratio of cFLIP and caspase 8 was directly correlated to resistance to anti CD 95 or TRAIL mediated apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Differences in the expression of downstream signalling molecules [ Fas associated death domain protein ( FADD ) , caspase 8 ] and inhibitors [ decoy receptor 1 ( DcR 1 ) , cellular FLICE like inhibitory protein ( c FLIP ) ] did not correlate with TRAIL sensitivity . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
FLIP [ Fas associated death domain protein ( FADD ) like interleukin 1 beta converting enzyme [ FLICE ( caspase 8 ) inhibitory protein ] ] , also modulate TRAIL signals , we determined whether chelerythrin affected TRAIL mediated apoptosis . ^^^ While TRAIL alone failed to activate caspase 8 or induce apoptosis , the addition of TRAIL to chelerythrin treated cells significantly enhanced cleavage of caspase 8 and apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Many neuroblastomas have hypermethylation and down regulation of CASP 8 , leading to resistance to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
RESULTS : Of 21 melanoma cell lines , 11 showed various degrees of sensitivity to TRAIL induced apoptosis through caspase 8 initiated cleavage of caspase 3 and DNA fragmentation factor 45 . ^^^ The remaining cell lines and primary cultures were resistant to TRAIL , but cisplatin , chemptothecin , and etoposide sensitized the resistant cell lines and primary cultures to TRAIL induced apoptosis , which also occurred through the caspase 8 initiated caspase cascade . ^^^ CONCLUSIONS : The results presented here indicate that cisplatin inhibits c FLIP protein expression and phosphorylation to restore TRAIL induced caspase 8 initiated apoptosis in melanoma cells , thus providing a new combined therapeutic strategy for melanomas . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL induced apoptosis in HT 29 cells was characterized by an increase in the percentage of cells in the sub G 1 fraction by flow cytometry , nuclear condensation and the activation of caspase 8 and caspase 3 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
SBHA appeared to sensitize melanoma to TRAIL induced apoptosis by up regulation of pro apoptotic proteins in the TRAIL induced apoptotic pathway such as caspase 8 , caspase 3 , Bid , Bak , and Bax , and up regulation of the BH 3 domain only protein , Bim . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Pre treatment with 12 O tetradecanoylphorbol 13 acetate ( PMA ) led to inhibition of TRAIL induced apoptosis in HeLa cells , which was characterized by a reduction in phosphatidylserine ( PS ) externalization , decreased caspase 8 processing , and incomplete maturation and activation of caspase 3 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
An RNase protection assay showed , in the rebamipide administered group , significantly decreased mRNA levels of apoptosis related genes such as caspase 8 , FasL , Fas , TRAIL and various cytokines genes such as IFN gamma , RANTES , TNF alpha , TNFR p 75 , IL 1beta . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In comparison , cell death using TRAIL ligand caused caspase 8 processing prior to cytochrome c release and executioner caspases and cell death was only partially rescued by Bcl 2 and Bcl xL overexpression . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 negative cells show very low rates of apoptosis after prolonged stimulation with TRAIL . ^^^ However , the combination of TRAIL and irradiation clearly lead to a combined effect in caspase 8 negative Jurkat cells , albeit with reduced death rates . ^^^ CONCLUSION : Our data show that a combined therapy with TRAIL and irradiation will only be effective in cells expressing at least one agonistic TRAIL receptor , FADD and caspase 8 or caspase 10 . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Western blotting analysis revealed that both TRAIL and glucose starvation induced Bid cleavage and FLIP degradation following caspase 8 activation in a time dependent manner , and ARK 5 overexpression clearly delayed Bid cleavage , FLIP degradation , and caspase 8 activation . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Further analysis demonstrated that inhibition of Fas ligand , tumor necrosis factor alpha , or TRAIL signaling with blocking reagents did not affect fenretinide induced apoptosis , raising the possibility that fenretinide activates caspase 8 in a death receptor independent manner . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 inhibition protects both CPT 11 pretreated wild type and Bax / HCT 116 cells from TRAIL induced apoptosis , whereas caspase 9 inhibition only rescued the wild type HCT 116 cells from death induced by TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL induced apoptosis through death receptor 5 ( DR 5 ) and was mediated by caspase 8 initiated extrinsic and intrinsic mitochondrial pathways in sensitive glioma cell lines . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
FLIP ( FLICE ( FAS associated death domain like IL 1beta converting enzyme ) inhibitory protein ) ) was identified as an inhibitor of FAS and TRAIL signals . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
FB 1 did not alter CD 95 expression in either strain ; however , expressions of TRAIL , and downstream signaling factors FADD , TRADD , and caspase 8 were higher in FB 1 treated TKO mice than in the corresponding WT animals . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In chemosensitive FL cells , we found that DNA damaging drugs promote apoptosis through p 53 dependent upregulation of the TRAIL DR 5 receptor , resulting in activation of caspase 8 and downstream executioner caspases , thereby evading bcl 2 mediated suppression of apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Furthermore , TRAIL sensitization was associated with increased proteolytic procession of caspase 8 and its downstream target BID , and z IETD FMK , the inhibitor specific to active caspase 8 totally blocked LiCl induced TRAIL sensitization . ^^^ These results indicate that GSK 3beta suppression sensitizes prostate cancer cells to TRAIL induced apoptosis that is dependent on caspase 8 activities but independent of NF kappaB activation , and suggest that a mechanism involving GSK 3beta activation may be responsible for TRAIL resistance in prostate cancer cells . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
However , the active form of caspase 8 was recruited to FADD and only sensitive cells showed increased caspase 8 activity upon TRAIL stimulation . ^^^ The caspase 8 specific inhibitor , Z IETD , impaired caspase 8 activation and completely abrogated TRAIL induced apoptosis . ^^^ These results suggest that TRAIL resistance in B lymphocytic leukaemia cells is due to negative regulation at the level of caspase 8 activation and that caspase 8 activation is an indispensable process in TRAIL induced apoptosis . ^^^ Interestingly , in some cell lines , TRAIL sensitivity and caspase 8 activity was enhanced or restored with the treatment of cycloheximide ( CHX ) . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Lower level of constitutive caspase 8 expression in the CEM cell line led to a poor response to both TRAIL induced activation of caspase 3 and reduction in the mitochondrial membrane potential ( DeltaPsim ) . ^^^ In summary , our data suggest that the leukemic cells resistance to TRAIL induced apoptosis might be due to the deficiency in the constitutive caspase 8 expression . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Interferon gamma and glucocorticoid modulated the expression of TRAIL on T cells of SLE patients and also modulated the expression of cellular Fas associating protein with death domain like interleukin 1 beta converting enzyme ( FLICE ) inhibitory protein ( cFLIP ) , an inhibitor of death receptor signaling , in neutrophils . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Restoration of TRAIL induced apoptosis in a caspase 8 deficient neuroblastoma cell line by stable re expression of caspase 8 . ^^^ The recently observed deregulation of caspase 10 in these cells prompted us to investigate the particular contribution of caspase 8 silencing in the resistance to TRAIL in N type cells . ^^^ Interestingly , the apoptotic response to TRAIL was enhanced by co treatment of SH EP and IGR N 91 C8 cells with CHX or with sub toxic concentration of doxorubicin ( DOX ) in a caspase dependent manner , as cells could be protected from death by specific caspase 8 or pan caspase inhibitors . ^^^ CHX or DOX was shown to enhance TRAIL induced caspase 8 activation and loss of mitochondrial transmembrane potential . ^^^ In conclusion , restoration of active caspase 8 expression in caspase 8 and caspase 10 deficient IGR N 91 cell line is necessary and sufficient to fully restore TRAIL mediated cell death . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL induced apoptosis is negatively regulated by numerous cellular factors including decoy receptors , cellular FADD like interleukin 1 beta converting enzyme ( FLICE ) interacting protein ( cFLIP ) , cellular inhibitor of apoptosis protein ( cIAP ) , 10 linked IAP ( XIAP ) , survivin , and NF kappaB . ^^^
Interacting proteins: P50591 and Q14790	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 . ^^^
Interacting proteins: P50591 and Q14790	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 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The combined use of HDACIs and TRAIL in suboptimal concentrations induced Bid cleavage and activation of caspase 8 , 10 , 3 , and 9 . ^^^ Human recombinant DR5 / Fc chimera protein , zVAD fmk pancaspase inhibitor , and caspase 8 and 10 inhibitors efficiently reduced apoptosis induced by cotreatment with HDACIs and TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
IG 20 ( MADD splice variant 5 ) , a proapoptotic protein , interacts with DR4 / DR5 and enhances TRAIL induced apoptosis by increasing recruitment of FADD and caspase 8 to the DISC . ^^^ 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 Q14790	Pubmed	SVM Score :0.0
The late phase of the TRAIL induced NF kappaB is critically dependent on caspase 8 and can be blocked by pharmacological and genetic inhibitors of caspase 8 activation , such as benzyloxycarbonyl VAD fluoromethyl ketone , benzyloxycarbonyl IETD fluoromethyl ketone , and small interfering RNA targeting caspase 8 and FADD . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Parthenolide induced phosphorylation of Bid and increased TRAIL dependent cleavage of Bid without affecting caspase 8 activities . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Also , combination treatment with BetA and TRAIL resulted in increased cleavage of caspase 8 and Bid indicating that activation of effector caspases may feed back in a positive amplification loop . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Chromatin immunoprecipitation and luciferase reporter analyses showed that c myc binds and represses the human FLIP promoter . c myc expression enhanced TRAIL induced caspase 8 cleavage and FLIP cleavage at the death inducing signaling complex . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL at 500 ng / ml induced significant DNA fragmentation , activation of caspase 8 and 3 , the processing of a proapoptotic BID , and mitochondrial release of cytochrome c in HL 60 / Vect cells , whereas no such events were observed in the HL 60 / FAK cells . ^^^ In particular , the expression of procaspase 8 gene and subsequent cleavage of caspase 8 were markedly reduced in HL 60 / FAK cells , while expression of TRAIL receptor 2 and 3 , TRADD , and FADD was equivalent in both types of cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The increased sensitivity of the XIAP shRNA cells to killing by TRAIL and taxanes correlated with enhanced caspase cleavage and activation , including caspase 8 , and robust processing of poly ( ADP ribose ) polymerase and BID compared to U 6 cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Coexposure of cells to marginally toxic concentrations of TRAIL and FP ( 24 h ) synergistically increased mitochondrial injury ( eg , cytochrome c , AIF , Smac / DIABLO release ) , cytoplasmic depletion of Bax , activation of Bid as well as caspase 8 and 3 , PARP cleavage , and apoptosis . ^^^ Coadministration of TRAIL markedly increased FP induced apoptosis in leukemic cells ectopically expressing Bcl 2 , Bcl 10 ( L ) , or a phosphorylation loop deleted form of Bcl 2 ( DeltaBcl 2 ) , whereas lethality was substantially attenuated in cells ectopically expressing CrmA , dominant negative FADD , or dominant negative caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
FLICE inhibitory protein ( c FLIP ) is an important regulator of TRAIL induced apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Instead , in the presence of DcR 3 , TRAIL engagement resulted in an increased activation of caspase 8 , an elevated cleavage of Bid , and enhanced release of Smac and cytochrome c from mitochondria to cytosol compared with TRAIL alone . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Here we show a novel mechanism by which FLICE like inhibitory protein ( c FLIP ) regulates apoptosis induced by tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) and one of its receptors , DR 5 . c FLIP is a critical regulator of the TNF family of cytokine receptor signaling . c FLIP has been postulated to prevent formation of the competent death inducing signaling complex ( DISC ) in a ligand dependent manner , through its interaction with FADD and / or caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Death receptor ( DR ) 4 or 5 , on binding to its ligand , tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , triggers apoptosis via activating the caspase 8 mediated caspase cascade . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Cell cycle analysis and quantification of Caspase 8 and TRAIL were used to identify apoptosis . ^^^ RESULTS : Treatment with Ad / TRAIL F / RGD resulted in significantly less cell viability , increased Caspase 8 and TRAIL activity , and a greater apoptotic fraction than treatment with PBS or Ad / CMV GFP . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In HT 29 cells studied further , rapid cleavage of caspase 8 , caspase 3 , Bid , and the caspase substrate poly ( ADP ribose ) polymerase occurred when CKI 7 and TRAIL were combined . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
After combined TRAIL and ethanol treatment , a potentiation of caspase 8 , 9 , 3 activation , a proapoptotic Bid protein cleavage , a decrease of mitochondrial membrane potential , a complete poly ( ADP ) ribose polymerase cleavage , and disappearance of antiapoptotic Mcl 1 protein were demonstrated . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
After having analysed the dose response for TRAIL induced activation of caspase 8 , 9 , 3 , breakdown of the mitochondrial membrane potential , and changes in the apoptotic morphology in cells expressing different Bcl 2 levels , we conclude that overexpression of Bcl 2 mediates a partial resistance towards lower doses of TRAIL that can be overcome when higher doses of TRAIL are applied . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Our results demonstrated that 16 genes ; bad , bax , bcl 2 , bcl w , bcl 10 , caspase 3 , caspase 7 , caspase 8 , c myc , E 124 , GADD 45 , mdm 2 , NKkappab 1 , p 53 , p 21 , Rb and trail were up regulated and six genes ; caspase 1 , caspase 2 , DR 5 , E2F1 , FasL and iNOS did not changed in response to DES treatment in wild type mice compared to p53+ / knockout mice . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The majority of high risk neuroblastomas lack the expression of caspase 8 due to gene silencing which suggest a mechanism for the selection of tumour cells that are refractory to multiple cytotoxic drugs including tumour necrosis factor related apoptosis inducing ligand ( TRAIL ) . ^^^ Inhibitors of DNA methyltransferases and IFN gamma induce expression of caspase 8 , and sensitise some neuroblastoma cells to TRAIL mediated apoptosis . ^^^ In five of the neuroblastoma cell lines ( SHEP 1 , SK N AS , SK N FI , SH SY 5Y and Kelly ) , IFN gamma promoted TRAIL mediated cleavage of caspase 8 , initiating a caspase cascade involving caspase 7 and PARP followed by apoptosis . ^^^ In three of the cell lines [ SK N BE ( 2 ) , SK N DZ and IMR 32 ] caspase 8 expression was induced by IFN gamma , but the cells were still resistant to TRAIL mediated apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In vivo treatment with IFNgamma increased tumor expression of TRAIL receptors and caspase 8 , but did not increase the antitumor effect of TRAIL receptor agonists on primary tumors . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The adaptor protein Fas associated death domain ( FADD ) and caspase 8 are essential for assembly of the death inducing signaling complex , and defects in either of these molecules can lead to TRAIL resistance . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Since it has been previously demonstrated that HIV 1 Tat protein up regulates the expression of TRAIL in monocytic cells whereas tat expressing lymphoid cells are more resistant to TRAIL cytotoxicity , we next investigated the effect of Tat on the expression / activity of both apical caspase 8 and 10 , which play a key role in mediating the initial phases of apoptosis by TRAIL , and c FLIP . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
These data suggest that amiloride sensitizes both tumor cells to TRAIL induced apoptosis by promoting Akt dephosphorylation and caspase 8 activation via the intracellular acidification and that Na ( + ) / H ( + ) exchanger inhibitors may play an important role in the anti cancer activity of TRAIL , especially , in TRAIL resistant tumors with highly active and expressed Akt . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
HDAC inhibitors sensitized resistant cells to TRAIL induced apoptosis by facilitating formation of an active death inducing signalling complex ( DISC ) , leading to the rapid activation of caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We show that Bid , a cytoplasmic Bcl 2 homology domain 3 containing protein activated by caspase 8 in response to TRAIL ligation , is essential for TRAIL etoposide apo ptotic synergy and , furthermore , that exposure to DNA damage primes cells to induction of apoptosis by otherwise sublethal levels of activated Bid . ^^^ Finally , we show that the extensive caspase 8 cleavage seen during TRAIL etoposide synergy is a consequence and not a cause of the apoptotic cascade activated downstream of Bid . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Bcl 2 overexpression attenuated TRAIL induced cleavage of caspase 8 , indicating its activation upstream and downstream of mitochondria , as well as cleavage of Bid and caspase 3 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL signals through its receptors DR 4 and DR 5 , which can activate caspase 8 as well . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In neuroblastoma cells with increased expression of N Myc , TRAIL triggers high levels of caspase 8 activation and Bid cleavage , leading to release of cytochrome c and Smac / DIABLO from mitochondria . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induces programmed cell death through the caspase activation cascade and translocation of cleaved Bid ( tBid ) by the apical caspase 8 to mitochondria to induce oligomerization of multidomain Bax and Bak . ^^^ Here we showed that , besides the specific cleavage and activation of Bid by caspase 8 and caspase 3 , TRAIL induced apoptosis in Jurkat T cells required the specific cleavage of Mcl 1 at Asp 127 and Asp 157 by caspase 3 , while other prototypic antiapoptotic factors such as Bcl 2 or Bcl 10 ( L ) seemed not to be affected . ^^^ These results suggested that removal of N terminal domains of Bid by caspase 8 and Mcl 1 by caspase 3 enabled the maximal mitochondrial perturbation that potentiated TRAIL induced apoptosis . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Analysis of TRAIL induced death inducing signaling complex ( DISC ) formation demonstrated enhanced formation of the DISC , enhanced cleavage of caspase 8 and cleavage of Bid in the presence of DRB , thereby facilitating the release of proapoptotic factors from the mitochondria with subsequent downregulation of the expression of XIAP and c IAP 1 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Huh 7 cells are resistant to TRAIL , despite the induction of caspase 8 after TRAIL engagement . ^^^ However , HCV core protein induces TRAIL apoptosis signaling via sequential induction of caspase 8 , Bid cleavage , activation of mitochondrial pathway , and effector caspase 3 . ^^^ Therefore , the HCV core protein induced TRAIL mediated apoptosis is dependent upon activation of caspase 8 downstream pathway to convey the death signal to mitochondria , leading to activation of mitochondrial signaling pathway and breaking the apoptosis resistance . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
To examine molecular mechanisms in cell resistance , we analyzed TRAIL induced DISC in TRAIL sensitive melanoma cells and showed that apoptosis initiating caspase 8 and caspase 10 were recruited to the DISC where they became activated through autocatalytical cleavage , leading to apoptosis through cleavage of downstream substrates such as caspase 3 and DFF 45 . ^^^ In TRAIL resistant melanoma cells , however , c FLIP proteins were recruited to the DISC , resulting in the inhibition of caspase 8 and caspase 10 cleavage in the DISC . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL activated the extrinsic ( cleavage of caspase 8 , caspase 3 and PARP ) and mitochondrial apoptotic pathways and reduced FLIP levels . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Additional intracellular factors leading to TRAIL resistance affect the caspase 8 / c FLIP ratio , such as loss of caspase 8 and caspase 10 due to mutations or gene methylation , CARP dependent degradation of active caspase 8 and changes in caspase 8 or c FLIP expression levels . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
APAF 1 , could not be proven in dystrophin deficient muscle , this study searches for other prospective candidates that may directly trigger apoptotic cell degradation by mitochondria independent pathways involving the interaction of tumour necrosis factor alpha ( TNF alpha ) and TRAIL with death receptors and subsequent activation of caspase 8 . ^^^ The expression of TNF alpha , TNF R 1 , TRAIL , NF ( kappa ) B and caspase 8 were studied in muscle biopsy specimens from 14 patients with a dystrophinopathy [ 10 Duchenne muscular dystrophies ( DMD ) , 2 Becker MD , and 2 DMD carriers ] by immunohistochemistry and Western blotting . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Western blot analysis showed that the hypoxia augmented TRAIL induced PARP cleavage as well as the activation of caspase 8 and caspase 3 , but not caspase 9 . ^^^
Interacting proteins: P50591 and Q14790	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 ) . ^^^ Expression of caspase 8 and NF kappaB suggests that signaling of TNFalpha and TRAIL minimally affects the biological properties of odontogenic epithelial components . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Activation of PKC seemed to mediate its effects upstream of mitochondria but downstream of caspase 8 and Bid in that pretreatment with PMA did not cause significant changes in the expression levels of TRAIL death receptors , alterations in the levels of caspase 8 activation , or cleavage of Bid . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
To further investigate the cellular mechanism of this effect , we found that E1A enhances TRAIL induced activation of caspase 8 , caspase 9 , and caspase 3 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Ras transformation enhanced TRAIL induced activation of caspase 8 by increasing its recruitment to TRAIL receptors . ^^^ The expression of constitutively activated mitogen activated protein kinase kinase 1 enhanced caspase 8 recruitment and sensitized immortalized human embryonic kidney cells to TRAIL induced death . ^^^ These results indicate that in normal human cells the TRAIL induced apoptotic signal is blocked at the level of caspase 8 recruitment and that this block can be eliminated by Ras transformation , involving activation of the mitogen activated protein kinase pathway . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
This might be especially important in systems where only low TRAIL concentrations are supplied that are not sufficient for the fast recruitment of caspase 8 to the DISC . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Analysis of the TRAIL pathway revealed that caspase 8 processing was enhanced in a p 21 dependent fashion in cells exposed to TRAIL and bortezomib as compared with cells treated with TRAIL alone . ^^^ These data strongly suggest that p 21 mediated cdk inhibition promotes TRAIL sensitivity via caspase 8 activation and that TRAIL and bortezomib should be combined in appropriate in vivo models as a possible approach to solid tumor therapy . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The combined use of luteolin and TRAIL induced Bid cleavage and the activation of caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL ( 100 ng / ml ) with LY 294002 ( 20 micromol / l ) activated the extrinsic pathway , causing progressive cleavage of caspase 8 and caspase 3 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL induced caspase 8 activation , Bid processing , drop of DeltaPsi ( m ) , and poly ADP ribose polymerase ( PARP ) cleavage but not in caspase 9 activation , and these events were inhibited in HER2 / PI3K / Akt suppressed BT 474 cells , which on the other hand exhibited downregulation of Bcl xL and increased response to mitomycin C . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Tunicamycin and TRAIL cooperatively activated caspase 8 , 10 , 9 , and 3 and Bid cleavage and this activation was also blocked in the presence of the DR5 / Fc chimera . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
CK 2 inhibition also induced rapid cleavage of caspase 8 , 9 , and 3 , as well as the caspase substrate poly ( ADP ribose ) polymerase after TRAIL treatment . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Inhibitors of caspase 8 or overexpression of FLIP completely blocked apoptosis induced by actinomycin D plus TRAIL cotreatment . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Combining the Bcl 10 ( L ) siRNA with TRAIL protein treatment resulted in an increase in the percentage of apoptotic cells and increased cleavage of caspase 8 , caspase 9 , caspase 3 and PARP . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Here we show that TRAIL treated T47D and MDA MB 468 breast cancer cells fail to initiate detectable caspase 8 processing and , consequently , do not initiate TRAIL mediated apoptosis . ^^^ Concomitant treatment with CDDO or CDDO Im reverses the TRAIL resistant phenotype , promoting robust caspase 8 processing and induction of TRAIL mediated apoptosis in vitro . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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 Q14790	Pubmed	SVM Score :0.0
Overexpression of PKCepsilon inhibited the apoptosis induced by TRAIL , acting downstream of caspase 8 and upstream of Bid cleavage and cytochrome c release from the mitochondria . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Generation of ROS by CCCP was responsible for TRAIL induced Bax and caspase activation because scavenging ROS completely abrogated apical caspase 8 activation and further downstream events leading to cell death . ^^^ Uncoupling of mitochondria also facilitated TRAIL induced release of proapoptotic factors . 10 linked inhibitor of apoptosis overexpression abrogated TRAIL induced apoptosis in the presence of CCCP and decreased initiator procaspase 8 processing , indicating that additional processing of caspase 8 required initiation of a mitochondrial amplification loop via effector caspases . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL cleaves caspase 8 , 9 and 3 of AM 1 cells : a possible pathway for TRAIL to induce apoptosis in ameloblastoma . ^^^ By applying TRAIL in AM 1 cells , ameloblastoma cell line , for 24 h , we found that TRAIL cleaved caspase 8 , 9 and 3 , and lowered mitochondrial membrane potential ( Deltapsim ) , and markedly induced apoptosis in AM 1 cells ( 46 % ) . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
FADD DN inhibited caspase 8 activation induced by TRAIL in the transfectants of CM and NES2Y cells . ^^^
Interacting proteins: P50591 and Q14790	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 Q14790	Pubmed	SVM Score :0.0
Accelerated degradation of caspase 8 protein correlates with TRAIL resistance in a DLD 1 human colon cancer cell line . ^^^ Compared with the TRAIL susceptible DLD 1 cell line , TRAIL resistant DLD1 / TRAIL R cells have a low level of caspase 8 protein , but not its mRNA . ^^^ Suppression of caspase 8 expression by siRNA in parental DLD 1 cells led to TRAIL resistance . ^^^ Restoration of caspase 8 protein expression by stable transfection rendered the DLD1 / TRAIL R cell line fully sensitive to TRAIL protein , suggesting that the low level of caspase 8 protein expression might be the culprit in TRAIL resistance in DLD1 / TRAIL R cells . ^^^ Sequencing analysis of the caspase 8 coding region revealed a missense mutation that is present in both TRAIL sensitive and TRAIL resistant DLD 1 cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Activation of the apoptosis by TRAIL and radiation was shown by activation of caspase 9 , caspase 8 , caspase 3 , and poly ( ADP ribose ) polymerase and increased DNA sub G ( 1 ) accumulation . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Resistance to TRAIL is associated with defects in ceramide signaling that can be overcome by exogenous C 6 ceramide without requiring down regulation of cellular FLICE inhibitory protein . ^^^ Glucose withdrawal or paclitaxel increase intracellular ceramide , down regulate cellular FLICE inhibitory protein ( cFLIP ) , and sensitize cells to TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 mRNA and protein , an important factor in the TRAIL mediated death pathway , is present at low levels in human NPCs . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We here show that TRAIL resistance in GBM is a consequence of overexpression of the short isoform of the caspase 8 inhibitor , c FLICE inhibitory protein ( FLIP ( S ) ) , and that FLIP ( S ) expression is in turn translationally enhanced by activation of the Akt mammalian target of rapamycin ( mTOR ) p 70 S6 kinase 1 ( S6K1 ) pathway . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The main apoptotic signal stimulated by tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) streams through caspase 8 activation and evokes caspase 3 , a central apoptosis activator . ^^^ In this study , the status of caspase 8 and 3 in gastric cancer cells related to the anticancer effects of TRAIL was investigated . ^^^ The pretreatment amounts of caspase 8 and 3 in these cells were not predictors for the anticancer effect of TRAIL . ^^^ Caspase 8 activity 24 h after treatment with TRAIL was well correlated with the anticancer effect of TRAIL ( r=0 . 777 , p=0 . 0060 ) . ^^^ These results suggested that gastric cancer might be a good target of TRAIL therapy because the majority of tumor cells have intact caspase 8 expression . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
CONCLUSION : The inhibition of ubiquitin proteasome pathway can sensitize rheumatoid arthritis synovial fibroblast cells to TRAIL induced apoptosis , and the activation of caspase 8 and caspase 4 is necessary in this process . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Protein was extracted and analyzed by Western blot for expression of cleavage of TRAIL receptors ( death receptor ( DR ) 4 and 5 ) , caspase 3 , caspase 8 , and BID . ^^^ CONCLUSIONS : Inhibition of PI3K / Akt by RNA interference sensitizes resistant colon cancer cells to TRAIL induced cell death through the induction of TRAIL receptors and activation of caspase 3 and caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
We unveil a link between TRAIL signaling and alteration of membrane lipid homeostasis that occurs in parallel to apical caspase activation but does not take over the mode of cell death because of the concurrent activation of caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Supporting the crucial role of caspase 8 in par 4 promoted apoptosis we demonstrate that inhibition of caspase 8 considerably reduces TRAIL induced apoptosis in par 4 and mock transfected Jurkat clones and reverses the described molecular changes . ^^^ In conclusion , we here provide first evidence that expression of par 4 in neoplastic lymphocytes augments sensitivity to TRAIL induced cell death and outline the responsible molecular mechanisms , in particular the crucial role of caspase 8 activation . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Here , we show that , differently from glioma cell lines , glioblastoma multiforme tumors were resistant to TRAIL stimulation because they expressed low levels of caspase 8 and high levels of the death receptor inhibitor PED / PEA 15 . ^^^ 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 . ^^^ Exogenous caspase 8 expression was the main event able to restore TRAIL sensitivity in primary glioblastoma cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Adenovirus E1A reverses the resistance of normal primary human lung fibroblast cells to TRAIL through DR 5 upregulation and caspase 8 dependent pathway . ^^^ Thus , our results suggest that adenovirus E1A sensitizes P HLF cells to TRAIL induced apoptosis involving DR 5 upregulation and the caspase 8 dependent pathway . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Interferon alpha enhances TRAIL mediated apoptosis by up regulating caspase 8 transcription in human hepatoma cells . ^^^ However , co stimulation with IFNalpha doubled TRAIL mediated apoptosis and enzymatic caspase 8 activity . ^^^ The synergistic effect of TRAIL and IFNalpha could be blocked by inhibiting caspase 8 expression . ^^^
Interacting proteins: P50591 and Q14790	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 Q14790	Pubmed	SVM Score :0.0
Down regulation of TRAIL is correlated to an increase in the levels of the anti apoptotic c FLIP ( L ) and Mcl 1 proteins that are likely to be involved in the suppression of caspase 8 activation and apoptosis . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Upregulation of c FLIP ( L ) protein , an inhibitor of apoptosis induced by tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , correspond with inhibition of ATRA induced ( autocrine TRAIL mediated ) caspase 8 activation and apoptosis . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
These results indicate that c FLIP inhibits TRAIL independent , DR 5 and caspase 8 dependent apoptosis in response to chemotherapy in CRC cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The up regulation of death receptors and inhibition of cFLIP by HDAC inhibitors will increase the ability of TRAIL to induce apoptosis , due to enhance activation of caspase 8 , cleavage of Bid , and release of mitochondrial proteins to the cytosol , and subsequent activation of caspase 9 and caspase 3 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
TRAIL induced , but not SAHA induced , cell killing could be prevented by the caspase 8 inhibitor , z IEDT fmk . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Direct degradation of Mcl 1 by TRAIL activated caspase 8 or caspase 3 produces Mcl 1 free Bim that mediates a Bax dependent apoptotic cascade . ^^^ They also suggest that Mcl 1 may serve as a direct substrate for TRAIL activated caspases implying the existence of a novel TRAIL / caspase 8 / Mcl 1 / Bim communication mechanism between the extrinsic and the intrinsic apoptotic pathways . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Cleavage of caspase 8 and caspase 3 occurred in both TRAIL resistant and TRAIL sensitive cells . ^^^
Interacting proteins: P50591 and Q14790	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 Q14790	Pubmed	SVM Score :0.0
In the search of the molecular mechanisms involved in the sensitization activity of 3 , 3 ' diindolylmethane , we found that combined treatment of 3 , 3 ' diindolylmethane and TRAIL led to significant down regulation of the cellular FLICE inhibitory protein expression ( c FLIP ) . ^^^
Interacting proteins: P50591 and Q14790	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 Q14790	Pubmed	SVM Score :0.0
TRAIL sensitisation by arsenic trioxide is caspase 8 dependent and involves modulation of death receptor components and Akt . ^^^ The combination of ATO and TRAIL synergistically enhanced cleavage of caspase 8 , which was blocked by the caspase inhibitor IETD . fmk as well as in cells deficient for caspase 8 , suggesting a requirement for the death inducing signalling complex . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Potentiation of camptothecin induced apoptosis by TRAIL appears dependent on cooperation between extrinsic and intrinsic pathways , as documented by loss of the sensitization to apoptosis following reduction of caspase 8 after small interfering RNA transfection . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
It also induced TRAIL R 2 expression , accelerated the death inducing signaling complex formation and enhanced caspase 8 activation . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 is mainly located outside of caveolae , but TRAIL caused it to redistribute to the caveolin 1 enriched fractions where it was cleaved . ^^^ Using confocal microscopy , we found that DR 5 , caspase 8 , and caveolin 1 became progressively concentrated in blebs of plasmalemma as they formed in response to TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Activation of apoptosis by Ad / TRAIL F / RGD plus radiotherapy was demonstrated by activation of caspase 9 , caspase 8 , and caspase 3 and cleaved poly ( adenosine diphosphate ribose ) polymerase in vitro and TUNEL assay in vivo . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
As disruption of mitochondrial transmembrane potential ( DeltaPsim ) , Leu Glu His Asp ase ( IETD ase ) activity , and the appearance of hypodiploid DNA + cells were markedly suppressed in IFN gamma treated FLS in response to TRAIL , IFN gamma induced suppression was supposed to achieve at upstream of caspase 8 . ^^^ The authors tried to determine the responsible molecules ; however , expression of TRAIL receptors ; pro caspase 3 / 8 / 9 ; Fas associated death domain protein ( FADD ) ; tumor necrosis factor receptor 1 associated death domain protein ( TRADD ) ; silencer of death domain ( SODD ) ; FLICE inhibitory protein ( FLIP ) ; and Bcl 2 , Bcl xL , and Bax in FLS was not modulated by IFN gamma . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Furthermore , a tumor cell specific downregulation of the FLICE inhibitory protein ( FLIP ) was observed , constituting a new mechanism of TRAIL sensitivity restoration by HDAC 1 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
However , since after the heat shock FlipL / S processing was transient , events upstream of caspase 8 and FADD may be responsible of the long lasting enhanced TRAIL apoptosis observed after heat shock . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Unlike BJAB positive control cells , for each SLCL tested , cleavage and activation of caspase 8 was inhibited due to failed recruitment of FADD and caspase 8 to TRAIL receptors upon stimulation . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
The percentages of TRAIL pathway genes ( CASP 8 , TFRSF10C , and TFRSF10D ) methylated were 30 , 9 . 5 , and 36 . 4 % , respectively , in ependymomas and 50 , 50 , and 16 . 7 % , respectively , in choroid plexus papillomas . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In our current report , we used DLD 1 colorectal cancer cells stably transfected with the POX gene under the control of a tetracycline inducible promoter and found POX stimulated expression of tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , DR 5 and cleavage of caspase 8 . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Moreover , induction of caspase 8 activation by TRAIL or TRAIL plus CDDP / DXR was substantially prevented by dnJNK . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Induction of apoptosis after combined treatment with TRAIL receptor antibodies HGS ETR 1 and / or HGS ETR 2 ( 0 . 01 , 0 . 1 , 1 . 0 mg / ml ) and irradiation with 2 , 5 or 10 Gy was determined by fluorescence microscopy and Western blot analysis of caspase 8 and PARP . ^^^
Interacting proteins: P50591 and Q14790	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 . ^^^ A combination of G banding / spectral karyotyping and FISH further defined the loss or gain of gene copy of these genes and further showed the simultaneous loss of one copy of DR4 / DR5 , caspase 8 , Bid , and Smac in two near triploid cell lines that were resistant to the combination treatment with TRAIL and chemotherapy . ^^^ Loss of the caspase 8 locus was also detected in a primary culture in correlation with the culture resistance to the combined TRAIL and chemotherapy treatment . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Further , in Ca 922 and HSC 6 but not in HOC 313 , caspase 8 inhibitor restored loss of viability induced either with LY 294002 and TRAIL or even with etoposide alone . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Adenovirus mediated transfection of caspase 8 sensitizes hepatocellular carcinoma to TRAIL and chemotherapeutic agent induced cell death . ^^^ Caspase 8 belongs to the cysteine protease family and is known to be activated at the initial step in the cascade of TRAIL induced apoptosis . ^^^ These results suggest both that exogenous over expression of caspase 8 by Adv Casp 8 may be essential for induction of HCC cell death and that the combination of Adv Casp 8 and TRAIL or chemotherapeutic agents could provide a useful strategy for treatment of HCC . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Interestingly , TRAIL neutralizing antibody protected tsAM5D cells from the temperature shift induced apoptotic cell death by blocking the activation of caspase 8 and 3 , indicating the involvement of TRAIL mediated death signaling in the temperature shift induced apoptosis . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) inhibited the TRAIL mediated activation of caspase 8 in tsAM5D cells exposed to 39 degrees C and cooperated with basic fibroblast growth factor and ciliary neurotrophic factor . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
In contrast , cleavage of caspase 8 , which is predominantly activated by the death receptor pathway , is a TNF related , apoptosis inducing ligand ( TRAIL ) induced late event in NDV mediated apoptosis of tumor cells . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Cotreatment with 15d PGJ ( 2 ) and TRAIL enhanced the sequential activation of caspase 8 , caspase 10 , caspase 9 , caspase 3 , and Bid . ^^^ DR5 / Fc chimera protein , zVAD fmk pancaspase inhibitor , and caspase 8 inhibitor efficiently blocked the activation of these apoptotic signal mediators and the induction of apoptotic cell death enhanced by cotreatment with 15d PGJ ( 2 ) and TRAIL . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Here , we report that TRAIL signaling in LNCaP prostate cancer cells stalled at downstream of caspase 8 and BID cleavage , as indicated by the lack of Bax translocation into mitochondria , and no subsequent activation of the caspase 9 cascade . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Interferon alpha enhances the level and / or the extent of activation of caspase 8 by TRAIL , thus providing a likely explanation for the sensitization of cells to the inhibition of translation . . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Role of caspase 8 and DR 5 in TRAIL induced apoptosis of neuroblastoma cells ] . ^^^ TRAILdouble ended arrow resistance of most neuroblastoma ( NB ) cell lines is related to the loss of caspase 8 expression and the expression and distribution of membrane TRAIL receptors . ^^^ This study investigated the role of caspase 8 and DR 5 in TRAIL induced apoptosis of NB cell line SKNDZ . ^^^ The SKNDZ cells expressing caspase 8 were not sensitive to TRAIL but those SKNDZ cells expressing both caspase 8 and DR 5 were sensitive . ^^^ CONCLUSIONS : SKNDZ cells expressing both caspase 8 and DR 5 restored the TRAIL sensitivity . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
Caspase 8 is silenced in a subset of highly malignant NB cells , which results in full TRAIL resistance . ^^^ In addition , despite constitutive caspase 8 expression , or its possible restoration by different strategies , NB cells remain weakly sensitive to TRAIL indicating a need to develop strategies to sensitise NB cells to TRAIL . ^^^ RESULTS : Sub toxic doses of HDACIs strongly sensitised caspase 8 positive NB cell lines to TRAIL induced apoptosis in a caspases dependent manner . ^^^
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
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Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA
Interacting proteins: P50591 and Q14790	Pubmed	SVM Score :0.0
NA