Caspase-8 (CASP8) in human and rodent cells facilitates the cleavage of receptor-interacting protein kinases RIPK1 and RIPK3 and prevents RIPK1/RIPK3-dependent regulated necrosis (Lin Y et al. 1999; Hopkins-Donaldson S et al. 2000). These cleavage sites are identified to be Asp324 in RIPK1 and Asp328 in RIPK3 in humans (Lin Y et al. 1999; Feng S et al. 2007). The lack of CASP8 proteolytic activity in the presence of viral (e.g. CrmA and vICA) or pharmacological caspase inhibitors results in necroptosis induction via RIPK1 and RIPK3 (Tewari M & Dixit VM 1995; Fliss PM & Brune W 2012; Hopkins-Donaldson S et al. 2000).
cysteine-type endopeptidase activity of active caspase-8 [cytosol]