Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin.
Fas/APO-1 and TNF receptor 1 share a common signaling motif in their cytoplasmic tail called the "death domain." Using the death domain as bait in the yeast two-hybrid system, several death domain-containing proteins that participate in cell death signaling have been identified. Here we report the isolation of a novel protein, sentrin, which interacts with Fas/APO-1 and TNF receptor 1 but not with FADD/MORT1 or CD40. Two-hybrid interaction assays reveal that sentrin associates only with the signal-competent forms of Fas/APO-1 or TNF receptor 1 death domains. Sentrin is a novel protein of 101 amino acids with homology to ubiquitin, Nedd8, and a Saccharomyces cerevisiae protein, Smt3. When overexpressed, sentrin provides protection against both anti-Fas/APO-1 and TNF-induced cell death.
Division of Molecular Medicine, The University of Texas-Houston Health Science Center 77030, USA.
T
T
Okura
L
L
Gong
T
T
Kamitani
T
T
Wada
I
I
Okura
C F
CF
Wei
H M
HM
Chang
E T
ET
Yeh
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000633:toxicity; D053200:Fas-Associated Death Domain Protein; D005656:Fungal Proteins / Q000378:metabolism / Q000494:pharmacology; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D000075687:NEDD8 Protein; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D014452:Ubiquitins / Q000378:metabolism / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism* / Q000633:toxicity*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D005656:Fungal Proteins; D000075687:NEDD8 Protein; C513172:Nedd8 protein, mouse; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D012097:Repressor Proteins; C099362:SMT3 protein, S cerevisiae; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014409:Tumor Necrosis Factor-alpha; D014452:Ubiquitins; D019014:fas Receptor