| Primary Identifier | IPR033170 | Type | Family |
| Short Name | Caspase-8 |
| description | Caspase-8 (MEROPS identifier C14.009) is a cytoplasmic cysteine endopeptidase with a preference for aspartyl bonds, acing at neutral pH []. It is active as a homodimer or as a heterodimer in association with the long isoform of FLICE, and proteolytic processing of the caspase-8 precursor is required for stabilisation of the dimer [, , ]. It is one of the activator caspases. Caspase-8 has a strict requirement for Asp in P1, a preference for Glu in P3 and small residues in P1' []. The caspase-8 proenzyme has two N-terminal death effector domains which are removed upon activation along with a linker region between the large and small subunits of the C-terminal catalytic domain. The death inducing signalling complex, composed of a transmembrane death receptor and the adapter protein FADD assembles at the cell membrane following binding of a death ligand. Procaspase-8 is recruited to this complex, and becomes active by dimerisation. Active caspase-8 can then activate the executioner caspases -3 and -7 [].Caspase-8 cleaves RIPK1, which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response. In humans, non-cleavable RIPK1 leads to autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response [, ]. |
