Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Apoptosis / drug effects*
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Apoptosis / immunology*
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Base Sequence
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / toxicity
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Fas-Associated Death Domain Protein
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Fungal Proteins / metabolism
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Fungal Proteins / pharmacology
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L Cells
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Mice
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Molecular Sequence Data
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NEDD8 Protein
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Protein Binding / immunology
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Protein Conformation
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Receptors, Tumor Necrosis Factor / metabolism*
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Repressor Proteins / pharmacology*
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SUMO-1 Protein
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Saccharomyces cerevisiae Proteins*
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Small Ubiquitin-Related Modifier Proteins
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / toxicity*
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Ubiquitins / metabolism
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Ubiquitins / pharmacology
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fas Receptor / metabolism*
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fas Receptor / toxicity*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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FADD protein, human
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Fadd protein, mouse
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Fas-Associated Death Domain Protein
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Fungal Proteins
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NEDD8 Protein
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Nedd8 protein, mouse
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins
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Repressor Proteins
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SMT3 protein, S cerevisiae
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SUMO-1 Protein
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Saccharomyces cerevisiae Proteins
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Small Ubiquitin-Related Modifier Proteins
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Tumor Necrosis Factor-alpha
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Ubiquitins
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fas Receptor