Reactome | FLIP(S) and procaspase-8 form heterodimer

FLIP(S) and procaspase-8 form heterodimer

Stable Identifier

R-HSA-3465429

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

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FLIP(S) and procaspase-8 form heterodimer

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The short form of cellular FLIP (FLIP(S) or c-FLIPS) has two death effector domains DEDs, which can bind to FADD and caspase-8 (CASP8). FLIP(S) protects the cells from apoptosis by inhibiting the processing of caspase-8 at the receptor level (Scaffidi C et al. 1999; Micheau O et al 2001).

FLIP(S) is a short-lived protein which is sensitive to ubiquitination and proteasomal degradation (Poukkula M et al. 2005;) Protein kinase C (PKC)- mediated phosphorylation of FLIP(S) at Ser193 was shown to prolongs the half-lives of FLIP(S) by inhibiting its polyubiquitination (Kaunisto A et al. 2009).

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
18190721	Association of TRAF2 with the short form of cellular FLICE-like inhibitory protein prevents TNFR1-mediated apoptosis Kim, DJ, Park, C, Oh, B, Kim, YY	J Mol Signal	2008
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