1. The TRAF3-binding site of human molluscipox virus FLIP molecule MC159 is critical for its capacity to inhibit Fas-induced apoptosis
- Author
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Margot Thome, M Thurau, Juerg Tschopp, M Tapernoux, and Helen Everett
- Subjects
TRAF3 ,Fas Ligand Protein ,CASP8 and FADD-Like Apoptosis Regulating Protein ,Apoptosis ,Biology ,Caspase 8 ,Fas ligand ,Cell Line ,Jurkat Cells ,Necrosis ,Viral Proteins ,Humans ,Caspase 10 ,Molecular Biology ,Binding Sites ,TNF Receptor-Associated Factor 3 ,Cell Biology ,Fas receptor ,TNF Receptor-Associated Factor 2 ,Cell biology ,Molluscipoxvirus ,Signal transduction ,Signal Transduction - Abstract
Members of the viral Flice/caspase-8 inhibitory protein (v-FLIP) family prevent induction of apoptosis by death receptors through inhibition of the processing and activation of procaspase-8 and -10 at the level of the receptor-associated death-inducing signaling complex (DISC). Here, we have addressed the molecular function of the v-FLIP member MC159 of the human molluscum contagiosum virus. MC159 FLIP powerfully inhibited both caspase-dependent and caspase-independent cell death induced by Fas. The C-terminal region of MC159 bound TNF receptor-associated factor (TRAF)3, was necessary for optimal TRAF2 binding, and mediated the recruitment of both TRAFs into the Fas DISC. TRAF-binding-deficient mutants of MC159 showed impaired inhibition of FasL-induced caspase-8 processing and Fas internalization, and had reduced antiapoptotic activity. Our findings provide evidence that a MC159/TRAF2/TRAF3 complex regulates a new aspect of Fas signaling, and identify MC159 FLIP as a molecule that targets multiple features of Fas-induced cell death.
- Published
- 2006