| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Ectopic expression of a dominant negative mutant of FADD , a cytoplasmic protein that mediates death signalling by Fas / Apo 1 and by TNF receptor type 1 ( TNFR 1 ) [ 6 9 ] , inhibited the induction of apoptosis by anti Fas / Apo 1 antibody , but had little effect on Apo 2L function . ^^^ These results suggest that Apo 2L activates a rapid , FADD independent pathway to trigger a cell death programme that requires the function of cysteine proteases such as ICE or CPP32 / Yama . . ^^^ Activation of apoptosis by Apo 2 ligand is independent of FADD but blocked by CrmA . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Transient expression of a dominant negative mutant of FADD impairs TNFR 60 mediated and Fas / Apo1 mediated apoptosis [ 13 ] [ 20 ] , but has no effect on TNF related apoptosis inducing ligand ( TRAIL / Apo2L ) induced cell death [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 21 ] . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| These families may include receptor / ligand molecules such as Fas , Fas ligand , tumor necrosis factor receptor 1 ( TNFR 1 ) , and TNF related apoptosis inducing ligand ( TRAIL ) ; signal transduction adapter molecules such as Fas associated death domain ( FADD ) , TNFR 1 associated death domain ( TRADD ) , receptor interacting protein ( RIP ) , Fas associated factor ( FAF ) , and Fas associated phosphatase ( FAP ) ; or effector molecules such as caspases . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| CD 95 , TNF related apoptosis inducing ligand ( TRAIL R 1 ) , and TRAIL R 2 bind FADD directly , whereas recruitment to TNF R 1 is indirect through another adaptor TNF receptor associated death domain protein ( TRADD ) . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Death receptor 4 ( DR 4 ) is a recently described receptor for the cytotoxic ligand TRAIL that reportedly uses a FADD independent pathway to induce apoptosis and does not activate the NF kappaB pathway . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| TRAIL receptors 1 ( DR 4 ) and 2 ( DR 5 ) signal FADD dependent apoptosis and activate NF kappaB . ^^^ Both TRAIL receptors bind the adaptor molecules FADD and TRADD , and both death signals are interrupted by a dominant negative form of FADD and by the FLICE inhibitory protein FLIP . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Pretreating the cells with neutralizing antibodies to Fas , tumor necrosis factor ( TNF ) alpha receptor 1 , or TNF related apoptosis inducing ligand receptors ( DR 4 and DR 5 ) did not affect taxol induced apoptosis , but transfection of the cells with a dominant negative FADD plasmid resulted in inhibition of taxol induced apoptosis , revealing that taxol induces apoptosis independently of these death receptors but dependently on FADD . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Because Fas associated protein with death domain ( FADD ) is the main adaptor for transmitting the Fas , TNF related apoptosis inducing ligand receptors , and TNF receptor 1 death signal , expression of FADD was analyzed by Western blot and immunocytochemistry in leukemic cells of 70 de novo AML patients treated with the European Organization of Research and Treatment of Cancer AML 10 randomized trial before initiation of induction chemotherapy . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| 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 ) . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Transfectants of human CM and NES2Y beta cell lines and primary islets transfected by FADD DN ( dominant negative form of Fas associated death domain ) , a mutant of FADD and / or a superrepressor of nuclear factor kappaB ( NF kappaB ) ( AdIkappaB ( SA ) 2 ) , were examined for their susceptibility to the TRAIL ( TNF related apoptosis inducing ligand ) induced death signal pathway , compared with controls , wild type cells , and vector transfectants in caspase fluorescence , Western blot , electrophoretic mobility shift , apoptosis , and cytotoxicity assays . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Overexpression of DEDD 2 induces moderate apoptosis and results in substantial sensitization to apoptosis induced by Fas ( CD95 / APO 1 ) , tumor necrosis factor related apoptosis inducing ligand ( TRAIL , Apo2L ) , or FADD . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| To investigate whether the cysteine protease dependent signaling of TRAIL leading to JNK activation is related to the apoptotic pathway engaged by this ligand , we investigated HeLa cells stably overexpressing a dominant negative mutant of FADD ( Fas associating protein with death domain ) ( GFP ( green fluorescent protein ) DeltaFADD ) . ^^^ These data suggest that cross linking of the TRAIL receptors and Apo1 / Fas , respectively , engages a FADD dependent pathway leading to the activation of apoptotic caspases and , in parallel , a FADD independent pathway leading to the stimulation of one or more cysteine proteases capable to activate JNK but not sufficient for the induction of cell death . . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Moreover , caspase 9S inhibited apoptosis induced by tumor necrosis factor ( TNF ) alpha , TNF factor related apoptosis inducing ligand ( TRAIL ) , Bax , or Fas associated death domain containing protein ( FADD ) as well as the combination of Apaf 1 and caspase 9 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Finally , the expression of additional apoptosis inducing genes , including tumor necrosis factor receptor ( TNFR ) , FADD , TRAIL , and DR 5 , was detected in mammalian testis . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Death signaling as well as JNK / SAPK activation by TRAIL in these cells is FADD and caspase dependent since dominant negative FADD or the caspase inhibitor zVAD prevented both , apoptosis and JNK / SAPK activity . ^^^ Therefore , activation of JNK / SAPKs by TRAIL or alphaAPO 1 occurs downstream of FADD and caspases and contributes to apoptosis in human lymphoid cell lines . . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| TRAIL receptor 2 signals apoptosis through FADD and caspase 8 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The activation of TRAIL receptors by ligand binding leads to apoptosis through caspase activation through an as yet unclear signaling pathway that does not require the FADD adaptor . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| In the presence of CHX , the stable overexpression of a deletion mutant of the Fas associated death domain molecule FADD comprising solely the death domain of the molecule but lacking its death effector domain ( FADD ( 80 208 ) ) led to the same response pattern as TRAIL or anti APO 1 treatment . ^^^ TRAIL , anti APO 1 , and FADD ( 80 208 ) initiated gene induction was blocked by a dominant negative mutant of TRAF 2 or the p 38 kinase inhibitor SB 203580 , similar to tumor necrosis factor receptor 1 induced NF kappaB activation . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| FADD is required for DR 4 and DR 5 mediated apoptosis : lack of trail induced apoptosis in FADD deficient mouse embryonic fibroblasts . ^^^ Using the FADD dominant negative molecule , several groups have reached different conclusions with respect to the role of FADD in TRAIL induced apoptosis . ^^^ We showed that FADD ( / ) MEF cells stably transfected with TRAIL receptors are resistant to TRAIL mediated cell death . ^^^ In contrast , TRAIL receptors stably transfected into heterozygous FADD ( + / ) cells or FADD ( / ) cells reconstituted with a FADD retroviral construct are sensitive to the TRAIL cytotoxic effect . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The TRAIL DISCussion : It is FADD and caspase 8 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| RESULTS : Although both S and N type cell lines express TRAIL R 2 , FADD , and caspases 3 and 10 , only S type cells express caspase 8 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| We have also shown that reactive iron ( Fe3+ ) and cGMP staining spatially resemble that of HO 1 ; which , in turn , colocalizes in motor neurons with transcription factors : Fas associated protein containing death domain ( FADD ) , tumor necrosis factor ( TNF ) related apoptosis inducing ligand ( TRAIL ) and p 53 . ^^^ Also , a site of injury directed pattern of induction of FADD , TRAIL , and p 53 immunoreactivity , and a widespread colocalization of the oncogenes with HO 1 protein , were found within motor neurons below the level of injury . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Both sensitive and resistant cell lines expressed TRAIL death receptor ( DR 5 ) , adapter protein Fas associated death domain ( FADD ) , and caspase 8 ; but resistant cell lines expressed 2 fold higher levels of the apoptosis inhibitor phosphoprotein enriched in diabetes / phosphoprotein enriched in astrocytes 15 kDa ( PED / PEA 15 ) . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| It is unclear whether FADD is required for TRAIL induced apoptosis . ^^^ FADD and caspase 8 , but not caspase 10 , are recruited to the receptor , and cells deficient in either FADD or caspase 8 blocked TRAIL induced apoptosis . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Whereas both S and N type cell lines express TRAIL R 2 , FADD , and caspase 3 and 10 , only S type cells express caspase 8 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 . ^^^ 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 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| METHODS : Five pancreatic cell lines were investigated for the expression of FasL / Fas , DcR 3 , DR 4 , DR5 / TRAIL , DcR 1 , DcR 2 , and other death pathways related molecules such as Bax , bcl xL , bcl 2 , FADD , and caspase 3 by flow cytometry , immunoblotting , and RT / PCR , both semiquantitative and real time ( TaqMan ) . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| Moreover , when keratinocytes with repressed NF kappaB activity were simultaneously treated with interferon gamma , there was a synergistic induction of apoptosis by TNF alpha that was dependent on FADD , tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) , and caspase activation . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| AZT and IFN alpha mediated apoptosis in PEL was blocked by stable overexpression of dominant negative Fas Associated Death Domain ( FADD ) , decoy receptor 2 ( DcR 2 ) , soluble TRAIL receptor fusion proteins ( DR 4 and DR 5 ) and thymidine . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Although the protein kinase inhibitor bisindoylmaleimide 8 increased apoptosis induced by agonistic anti Fas antibody , tumor necrosis factor alpha , and TRAIL , these effects were not observed with the protein kinase C inhibitor H 7 and were not associated with increased FADD recruitment to Fas . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| DAP 3 also associates with the pro caspase 8 binding adapter protein Fas associated death domain ( FADD ) , and links FADD to the TRAIL receptors DR 4 and DR 5 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| IFN gamma or TRAIL treatment alone did not change expression of other pro or antiapoptotic proteins such as DR 4 , DR 5 , FADD , Bax , IAP 1 , XIAP , Bcl 2 , and Bcl XL . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
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 Q13158 |
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 . ^^^ Here we show that caspase 10 is recruited not only to the native TRAIL DISC but also to the native CD 95 DISC , and that FADD is necessary for its recruitment to and activation at these two protein complexes . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| This activation is regulated by the recruitment of an adaptor protein Fas associating death domain ( FADD ) to TRAIL death receptors , death receptor 4 ( DR 4 , TRAIL R 1 ) and death receptor 5 ( DR 5 TRAIL R 2 ) . ^^^ 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 Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| Inhibition of the TNF or TRAIL signalling pathway with antagonistic antibodies or fusion proteins did not affect apoptosis induced by ErPC , and a dominant negative FADD construct did not abolish ErPC induced effects . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induced apoptosis is mediated by its receptors DR 4 ( TRAIL R 1 ) and DR 5 ( TRAIL R 2 ) and the adapter protein Fas associated death domain protein ( FADD ) . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| 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 ) . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Transfection of FADD DN in LNCaP resulted in inhibition of caspase activation as well as in resistance to combined treatment with TRAIL and wortmannin . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
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 . ^^^ 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 Q13158 |
Pubmed |
SVM Score :0.0 |
| In contrast , the serine protease inhibitor does not affect TRAIL induced death in prostate tumor cells suggesting that the FADD DD dependent pathway can be activated by TRAIL . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| We also found that , similarly to betaAP and TRAIL , activation of the death domain adaptor protein FADD results in neuronal cell death . ^^^ Lack of FADD function , by overexpression of its dominant negative , rescued cells from either TRAIL or betaAP induced neurotoxicity , supporting the hypothesis that these three molecules share common intracellular pathways . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Investigating the differences in TRAIL induced apoptotic pathways in HCT 116 and SW 480 cells revealed that although FADD , BID , and procaspase 3 protein levels are higher in SW 480 cells , and although procaspase 8 and FLIP processing is more efficient at the TRAIL DISC of SW 480 cells , BID , procaspase 3 , XIAP , and PARP cleavages occur more rapidly in HCT 116 , despite the higher levels of BCL 2 and HSP 70 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| An increased recruitment of Fas associated death domain ( FADD ) and procaspase 8 to the TRAIL induced death inducing signaling complex ( DISC ) was shown in cells exposed to anticancer drugs . ^^^ Importantly , besides mitochondrial potentiation , we show here that cytotoxic drugs sensitize HT 29 colon cancer cells to TRAIL induced cell death by enhancing FADD and procaspase 8 recruitment to the DISC , a novel mechanism whose efficacy could depend partly on Bcl 2 expression level . . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| TRAIL ligation induced DISC formation in TRAIL sensitive ( RD , Rh 18 , Rh 30 ) and TRAIL resistant RMS ( Rh 28 , Rh 36 , Rh 41 ) , with recruitment of FADD and procaspase 8 . ^^^ In RD cells , overexpression of dominant negative FADD ( DNFADD ) completely abolished TRAIL induced cell death in contrast to dominant negative caspase 8 ( DNC 8 ) , which only partially inhibited TRAIL induced apoptosis , growth inhibition , or loss in clonogenic survival . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
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 Q13158 |
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 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| PS 341 treatment by itself does not affect the levels of Bax , Bak , caspases 3 and 8 , c Flip or FADD , but elevates levels of TRAIL receptors DR 4 and DR 5 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| This was confirmed by analysis of TRAIL death inducing signaling complex formation , which was disrupted in PMA treated cells as evidenced by a marked reduction in Fas associated death domain protein ( FADD ) recruitment , an effect that could not be explained by any change in FADD phosphorylation state . ^^^ In an in vitro binding assay , the intracellular domains of both TRAIL R 1 and TRAIL R 2 bound FADD : activation of PKC significantly inhibited this interaction suggesting that PKC may be targeting key apical components of death receptor signaling . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Presence of FADD was found to be essential for TRAIL induced apoptosis . ^^^ No combined effects of TRAIL with irradiation could be found in FADD DN overexpressing and FADD deficient cells . ^^^ 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 Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| DR 5 was internalized into the cytoplasm where it recruited FAS associated death domain protein ( FADD ) under TRAIL stimulation in both sensitive and resistant cells . ^^^ However , the active form of caspase 8 was recruited to FADD and only sensitive cells showed increased caspase 8 activity upon TRAIL stimulation . ^^^ However , FADD like interleukin 1 beta converting enzyme inhibitory protein ( c FLIPL ) was similarly expressed and down regulated after TRAIL stimulation in both sensitive and resistant cells . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| TRAIL mediated MO3 . 13 cell apoptosis was abrogated by the dominant negative form of the adaptor protein FADD and by caspase inhibitors . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| Inhibitors directed against caspases 2 , 3 , 8 , and 9 reduced the synergistic apoptotic response following low dose UV light plus TRAIL exposure ; as did forced over expression of Bcl 10 and dominant negative ( DN ) constructs of FADD and caspase 9 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Although there is much interest in TRAIL , the mechanism by which FADD is recruited to the TRAIL receptors is not clear . ^^^ FADD deficient Jurkat cells stably expressing these FADD mutations did not transduce TRAIL or Fas / CD95 signaling . ^^^ We conclude that in contrast to current models where the death domain of FADD functions independently of the death effector domain , the death effector domain of FADD comes into direct contact with both TRAIL and Fas / CD95 receptors . . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| Dominant negative FADD and p 53 siRNA inhibited the synergistic interaction between irradiation and TRAIL . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| In particular , the expression of procaspase 8 gene and subsequent cleavage of caspase 8 were markedly reduced in HL 60 / FAK cells , while expression of TRAIL receptor 2 and 3 , TRADD , and FADD was equivalent in both types of cells . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The C terminal tails of tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) and Fas receptors have opposing functions in Fas associated death domain ( FADD ) recruitment and can regulate agonist specific mechanisms of receptor activation . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Incubation with DcR 3 did not increase the surface expression of TRAIL receptor , and the level of Fas associated death domain protein and cellular FLICE like inhibitory protein was not altered . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 . ^^^ To the contrary , TRAIL treatment released c FLIP ( L ) from DR 5 , permitting the recruitment of FADD to the active DR 5 signaling complex . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Western blotting analyses revealed that IFN gamma dramatically increased the protein levels of interferon regulatory factor ( IRF ) 1 , but not TRAIL receptors ( DR 4 and DR 5 ) and pro apoptotic ( FADD and Bax ) and anti apoptotic factors ( Bcl 2 , Bcl XL , cIAP 1 , cIAP 2 and XIAP ) . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The pattern of basal TRAIL receptor expression , decoy receptors , FLIP and FADD could not be correlated with resistance or sensitivity to TRAIL induced apoptosis . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 . ^^^ Overexpression of cellular FADD like interleukin 1beta converting enzyme inhibitory protein ( cFLIP ) correlates with TRAIL resistance in several types of cancer . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The mechanism of cell death by p53p Ant was through the FADD / caspase 8 dependent pathway without the involvement of the TRAIL pathway , Bcl 2 family and cell cycle changes . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The major finding are as following : ( 1 ) The mechanical stretch activated death receptor mediated apoptotic signaling in cardiomyocytes , including activation of caspases 8 , 9 and 3 , up regulation of Fas , FasL expression and cell surface trafficking of death ligands ( FasL and TRAIL ) ; ( 2 ) That exogenous death ligand ( TRAIL ) enhanced , while soluble death receptor ( sDR 5 ) neutralized , stretch induced apoptosis ; ( 3 ) Adenovirus delivered dominant negative FADD ( FADD DN ) significantly reduced apoptosis , caspases 8 , 9 , and 3 activation , and stretch induced cyt c release from mitochondria . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| Extensive regions of the FADD death domain are required for binding to the TRAIL receptor DR 5 . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| In conclusion , these results show that otherwise chemotherapy resistant tumor cells can be sensitized for TRAIL induced apoptosis at the DISC level in the presence of high levels of cFLIP , which suggests the existence of an additional factor that modulates the interaction of FADD and the TRAIL death receptors . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| Some members of the DR family , CD 95 and the TRAIL receptors DR 4 and DR 5 , directly bind FADD , whereas others , such as TNF receptor 1 and DR 3 , initially bind another adaptor protein , TRADD , which then recruits FADD . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| In contrast , FADD ( / ) Jurkat T cells are resistant to FasL and Trail but die of necrosis when incubated with TNF alpha . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The mechanism for this enhanced apoptosis involved induction of TRAIL and its interaction with death receptors , as blocking the death receptor pathway using dominant negative FADD , or by addition of neutralizing antibody against TRAIL , reduced the apoptotic response to IFN alpha and IFN gamma . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| We have shown that COX 2 inhibition sensitizes human colon carcinoma cells to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) induced apoptosis by inducing clustering of the TRAIL receptor DR 5 at the cell surface and the redistribution of the death inducing signaling complex components ( DR 5 , FADD , and procaspase 8 ) into cholesterol rich and ceramide rich domains known as caveolae . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The dominant negative FADD mutation ( FADD DN ) results revealed that the apoptosis in Ad E1A and Ad TRAIL coinfected P HLF cells was completely blocked following inhibition of the death receptors associated apoptosis inducing molecules FADD . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| 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 Q13158 |
Pubmed |
SVM Score :0.0 |
| TRAIL induced apoptosis after heat shock was dependent on caspases and FADD and an enhanced FlipL / S processing was noticed . ^^^ 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 Q13158 |
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 Q13158 |
Pubmed |
SVM Score :0.0 |
| RESULTS : CGH detected loss of the chromosomal regions that contain the following genes : 8p12 p 23 ( DR 4 and DR 5 ) , 2q33 34 ( caspase 8 ) , 11q13 . 3 ( FADD ) , 22q11 . 2 ( Bid ) , and 12q24 . 1 q24 . 3 ( Smac / DIABLO ) in TRAIL resistant cell lines . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| The following genes were overexpressed in both hyperplasia and adenoma : CHEK 1 , ATM , BCL XL , FAS , TNF , cIAP 1 , TRAIL , FADD , CASP 4 , 5 , 6 , 8 , CD120b , CD 137 , LTA , TANK , TARF 2 , CAD , LIGHTR , DR3LG . ^^^ |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P50591 and Q13158 |
Pubmed |
SVM Score :0.0 |
| NA |
|