FLIP(L) and procaspase-8 form heterodimer in FasL/CD95 signaling

Stable Identifier
R-HSA-3465459
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Reaction
Species
Homo sapiens
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Pro-caspase-8 and FLIP(L) are recruited to FAS/CD95 receptor complex where 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 (Chang DW et al. 2002; Fricker N et al. 2010; Toivonen HT et al. 2011; Boatright KM et al. 2004; Okano H et al. 2003). 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
12215447 The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex

Thome, M, Grütter, MG, Briand, C, Schneider, P, Nicholson, DW, Holler, N, Tschopp, J, Micheau, O

J. Biol. Chem. 2002
20696707 Model-based dissection of CD95 signaling dynamics reveals both a pro- and antiapoptotic role of c-FLIPL

Richter, P, Lavrik, IN, Beaudouin, J, Fricker, N, Eils, R, Krammer, PH

J. Cell Biol. 2010
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
15289496 NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP

Kracht, M, Siegmund, D, Dittrich-Breiholz, O, Scheurich, P, Wajant, H, Häcker, G, Janssen, O, Kreuz, S, Samel, D, Rumpf, JJ, Leverkus, M

J. Cell Biol. 2004
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