Reactome | FLIP(L) and procaspase-8 form heterodimer in TRAIL signaling

FLIP(L) and procaspase-8 form heterodimer in TRAIL signaling

Stable Identifier

R-HSA-3371359

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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FLIP(L) and procaspase-8 form heterodimer in TRAIL signaling

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Pro-caspase-8 and FLIP(L) are recruited to the DISC. Following recruitment to the DISC, FLIP-L forms a heterodimer with caspase-8 through both death effector domain (DED) and caspase-like domain (CLD). In addition, FLIP(L) can also regulate signaling via interaction with the DED of FADD. The regulatory function of FLIP(L) has been found to differ depending on its expression levels. FLIP(L) was shown to inhibit death receptor (DR)-mediated apoptosis only when expressed at high levels, while low cell levels of FLIP(L) enhanced DR signaling to apoptosis (Sharp DA et al. 2005; Siegmund D et al. 2002; Boatright KM et al. 2004; Okano H et al. 2003; Yerbes R et al. 2011). The expression levels of c-FLIP proteins were shown to be regulated by NFkappaB signaling pathway (Micheau O et a. 2001; Kreuz S et al 2001).

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
20951169	Cellular FLIP(L) plays a survival role and regulates morphogenesis in breast epithelial cells Yerbes, R, Palacios, C, López-Rivas, A, Reginato, MJ	Biochim. Biophys. Acta	2011
11384965	Fas-associated death domain protein (FADD) and caspase-8 mediate up-regulation of c-Fos by Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via a FLICE inhibitory protein (FLIP)-regulated pathway Juo, P, Scheurich, P, Blenis, J, Reichwein, M, Siegmund, D, Thome, M, Tschopp, J, Mauri, D, Wajant, H, Peters, N	J. Biol. Chem.	2001
15760909	Selective knockdown of the long variant of cellular FLICE inhibitory protein augments death receptor-mediated caspase-8 activation and apoptosis Sharp, DA, Ashkenazi, A, Lawrence, DA	J. Biol. Chem.	2005