PROTECTION AGAINST FAS APO-1-MEDIATED 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 c ytoplasmic 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 inte racts with Fas/APO-1 and TNF receptor 1 but not with FADD/MORT1 or CD4 0, Two-hybrid interaction assays reveal that sentrin associates only w ith the signal-competent forms of Fas/APO-1 or TNF receptor 1 death do mains, Sentrin is a novel protein of 101 amino acids with homology to ubiquitin, Nedd8, and a Saccharomyces cerevisiae protein, Smt3, When o verexpressed, sentrin provides protection against both anti-Fas/APO-1 and TNF-induced cell death.