Artikel
The TRAF3 binding site of human molluscipox virus FLIP molecule MC159 is critical for its capacity to inhibit Fas-induced apoptosis
Suche in Medline nach
Autoren
-
Mathias Thurau
- Division for Molecular and Experimental Surgery, Clinical Center, University of Erlangen-Nuremberg, Deutschland
-
Helen Everett
- Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
-
Myriam Tapernoux
- Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
-
Jürg Tschopp
- Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
-
Margot Thome
- Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland
| Veröffentlicht: | 20. März 2006 |
|---|
Gliederung
Text
The tumorigenic virus Molluscum Contagiosum Virus (MCV) efficiently evades the immune system of the infected host, because it encodes proteins that either directly target certain aspects of the host immune response or it increase the resistance of the host cell to apoptosis. 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 pro-caspases-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 MCV. MC159 FLIP powerfully inhibited both caspase-dependent and caspase-independent cell death induced by Fas. The C-terminal region of MC159 bound TRAF3, 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 anti-apoptotic 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. Thus MC159 FLIP may contribute to the formation of the benign MCV tumors.
