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The Journal of Immunology, Vol 157, Issue 10 4277-4281, Copyright © 1996 by American Association of Immunologists

CUTTING EDGE

Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin

T Okura, L Gong, T Kamitani, T Wada, I Okura, CF Wei, HM Chang and ET Yeh
Division of Molecular Medicine, The University of Texas-Houston Health Science Center 77030, USA.

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.


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