The Long Form of FLIP Is an Activator of Caspase-8 at the Fas Death-inducing Signaling Complex

摘要: Death receptors, such as Fas and tumor necrosis factor-related apoptosis-inducing ligand recruit Fas-associated death domain pro-caspase-8 homodimers, which are then autoproteolytically activated. Active caspase-8 is released into the cytoplasm, where it cleaves various proteins including pro-caspase-3, resulting in apoptosis. The cellular domain-like interleukin-1-beta-converting enzyme-inhibitory protein long form (FLIP(L)), a structural homologue of lacking caspase activity because several mutations active site, potent inhibitor receptor-induced FLIP(L) proposed to block by forming proteolytically inactive heterodimer with caspase-8. In contrast, we propose that FLIP(L)-bound an protease. Upon heterocomplex formation, limited autoprocessing occurs generation p43/41 p12 subunits. This partially processed but also non-cleaved FLIP(L)-caspase-8 they both bind synthetic substrates efficiently. Moreover, expression favors receptor-interacting kinase (RIP) processing within Fas-signaling complex. We inhibits release-dependent pro-apoptotic signals, whereas single, membrane-restricted site acts on local RIP.