FLIP(L) and procaspase-8 form heterodimer

Stable Identifier
Reaction [binding]
Homo sapiens
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Heterodimerization with CFLAR is able to activate CASP8 and -10 because CFLAR uses the same dimer interface between the catalytic domains (Boatright et al. 2004; Dohrman et al. 2005; Micheau et al. 2002; Yu et al. 2009). However, the enzymatic activity of CFLAR:CASP8 heterodimers is insufficient to generate active CASP8 heterotetramers for the apoptosis induction in mammalian cells. In contrary, the residual catalitic activity of CASP8:CFLAR is sufficient for RIP1/RIP3 cleavage, which inhibited the necroptotic cell death mode (Feoktistova M et al. 2011; Dillon CP et al. 2012; Oberst A et al. 2001).

Literature References
PubMed ID Title Journal Year
11463813 NF-kappaB signals induce the expression of c-FLIP

Micheau, O, Lens, S, Gaide, O, Alevizopoulos, K, Tschopp, J

Mol. Cell. Biol. 2001
9880531 The role of c-FLIP in modulation of CD95-induced apoptosis

Scaffidi, C, Schmitz, I, Krammer, PH, Peter, ME

J. Biol. Chem. 1999
21235526 FLIP(L) induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity

Pop, C, Oberst, A, Drag, M, Van Raam, BJ, Riedl, SJ, Green, DR, Salvesen, GS

Biochem J 2011
21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms

Feoktistova, M, Geserick, P, Kellert, B, Dimitrova, DP, Langlais, C, Hupe, M, Cain, K, MacFarlane, M, H├Ącker, G, Leverkus, M

Mol. Cell 2011
Participant Of
Event Information
Orthologous Events