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

ReviewStatus

5/5

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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-life of FLIP(S) by inhibiting its polyubiquitination (Kaunisto A et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
9880531	The role of c-FLIP in modulation of CD95-induced apoptosis Krammer, PH, Peter, ME, Schmitz, I, Scaffidi, C	J. Biol. Chem.	1999
11463813	NF-kappaB signals induce the expression of c-FLIP Gaide, O, Micheau, O, Tschopp, J, Lens, S, Alevizopoulos, K	Mol. Cell. Biol.	2001
18190721	Association of TRAF2 with the short form of cellular FLICE-like inhibitory protein prevents TNFR1-mediated apoptosis Kim, YY, Oh, B, Park, C, Kim, DJ	J Mol Signal	2008
21235526	FLIP(L) induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity Drag, M, Van Raam, BJ, Oberst, A, Green, DR, Riedl, SJ, Salvesen, GS, Pop, C	Biochem J	2011