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

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

Stable Identifier

R-HSA-3465459

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 FasL/CD95 signaling

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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