title: Direct activation of caspase 8 by the proapoptotic E2 protein of HPV18 independent of adaptor proteins.
abstract: The self-activation of initiator caspases is dependent on their oligomerization driven by interaction with the death fold domains (DFD) of adaptor proteins. Here, we show that the E2 protein of human papillomavirus type 18 triggers apoptosis by assembling cytoplasmic filaments together with caspase 8, in which its efficient self-activation occurs. The E2 protein binds directly to the death effector domains (DED) of caspase 8 through non-DFD interaction. This interaction is independent of FADD, but it can cooperate with FADD homotypic binding to caspase 8 to induce its oligomerization; hence cell death, while it is antagonized by competitive binding of MC159 FLICE inhibitory protein. The amino-terminal domain of E2 contains a 27 amino-acid alpha-helix, which is necessary and sufficient to induce caspase oligomerization and cell death. Our results provide evidence for adaptor-independent oligomerization of caspase 8, mediated by non-DFD direct interactions with the HPV18 E2 protein, thus deciphering a new pathway for caspase 8 activation.
authors.affiliation: Unité Expression Génétique et Maladies, CNRS FRE 2850, Institut Pasteur, 25 rue du Dr Roux, Paris cedex 15, France.
authors.forename: F
authors.initials: F
authors.lastname: Thierry
authors.forename: C
authors.initials: C
authors.lastname: Demeret
mesh_terms: D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000201:enzymology / Q000648:ultrastructure / Q000821:virology; D004789:Enzyme Activation; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D053200:Fas-Associated Death Domain Protein; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins; C069102:oncogene protein E2, Human papillomavirus type 18; D053181:Caspase 8