activated TLR3/TLR4:TRIF:RIP1:FADD active caspase-8 activated TLR3/TLR4:TRIF:RIP1:FADD:pro-caspase-8 Caspase-8 processing Authored: Shamovsky, V, 2012-05-15 EC Number: 3.4.22 Edited: Shamovsky, V, 2012-11-19 GENE ONTOLOGYGO:0008624 Pubmed12181749 Pubmed12620240 Pubmed15814722 Pubmed19278658 Pubmed20308068 Pubmed21737330 Pubmed22421964 Reactome Database ID Release 432562564 Reactome, http://www.reactome.org ReactomeREACT_150381 Reviewed: Fitzgerald, Katherine A, 2012-11-13 TLR3/4 signaling component were shown to mediate apoptosis in various human cell lines in the FADD:caspasse-8-dependent manner [Kalai M et al 2002; Kaiser WJ and Offermann MK 2005; Estornes Y et al 2012]. Caspase-8 zymogens (procaspase-8) are present in the cells as inactive monomers, containing a large N-terminal prodomain with two death effector domains (DED), and a C-terminal catalytic subunit composed of small and a large domains separated by a smaller linker region [Donepudi M et al 2003; Keller N et al 2009]. Dimerization is required for caspase-8 activation [Donepudi M et al 2003]. The dimerization event occurs at the receptor signaling complex. Once dimerized, caspase-8 zymogen undergoes a series of autoproteolytic cleavage events at aspartic acid residues in their interdomain linker regions. A second cleavage event between the the N-terminal prodomain and the catalytic domain releases the active caspase from the activation complex into the cytosol. The resulting fully active enzyme is a homodimer of catalytic domains, where each domain is compsed of a large p18 and a small p10 subunit [Keller N et al 2009; Oberst A et al 2010].