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).
Thome, M, Grütter, MG, Briand, C, Schneider, P, Nicholson, DW, Holler, N, Tschopp, J, Micheau, O
Richter, P, Lavrik, IN, Beaudouin, J, Fricker, N, Eils, R, Krammer, PH
Juo, P, Scheurich, P, Blenis, J, Reichwein, M, Siegmund, D, Thome, M, Tschopp, J, Mauri, D, Wajant, H, Peters, N
Kracht, M, Siegmund, D, Dittrich-Breiholz, O, Scheurich, P, Wajant, H, Häcker, G, Janssen, O, Kreuz, S, Samel, D, Rumpf, JJ, Leverkus, M
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