Fas-associated Death Domain Protein Interleukin-1β-converting Enzyme 2 (FLICE2), an ICE/Ced-3 Homologue, Is Proximally Involved in CD95- and p55-mediated Death Signaling

• DOI: 10.1074/jbc.272.10.6578
• Publication Date: 2002-07-26T14:49:13Z
• Authors: Claudius Vincenz; Vishva M. Dixit
• Keywords: FADD; Caspase 8; Lipid raft

The pivotal discovery that Fas-associated death domain protein (FADD) interleukin-1β-converting enzyme (FLICE)/MACH was recruited to the CD95 signaling complex by virtue of its ability bind adapter molecule FADD established this protease has a role in initiating pathway (Boldin, M. P., Goncharov, T. M., Goltsev, Y. V., and Wallach, D. (1996) Cell 85, 803-815; Muzio, Chinnaiyan, A. Kischkel, K. C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, Bretz, J. D., Zhang, Gentz, R., Mann, Krammer, P. H., Peter, E., Dixit, V. 817-827). In report, we describe cloning characterization new member caspase family, homologue FLICE/MACH, Mch4. Since overall architecture function is similar FLICE, it been designated FLICE2. Importantly, carboxyl-terminal half small catalytic subunit includes amino acids predicted be involved substrate binding distinct. We show pro-domain FLICE2 encodes functional effector binds corresponding FADD. Consistent with finding, both p55 tumor necrosis factor receptor complexes FADD-dependent manner. A for suggested finding an active site mutant inhibits receptor-mediated apoptosis. therefore signal transduction.