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

Stable Identifier
Reaction [binding]
Homo sapiens
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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 TNF-R1 signaling via interaction with the DED of FADD. The regulatory function of FLIP(L) has been found to differ depending on its expression levels. c-FLIP 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 (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
20218968 c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-alpha-induced apoptosis

Vittori, D, Vota, D, Callero, M, Chamorro, ME, Nesse, A

Cell Biol. Int. 2010
18256533 TNF signaling gets FLIPped off: TNF-induced regulation of FLIP

Rushworth, SA, Taylor, A, Langa, S, MacEwan, DJ

Cell Cycle 2008
12620240 Insights into the regulatory mechanism for caspase-8 activation

Donepudi, M, Mac Sweeney, A, Briand, C, Grütter, MG

Mol. Cell 2003
18838202 Differential responses of FLIPLong and FLIPShort-overexpressing human myeloid leukemia cells to TNF-alpha and TRAIL-initiated apoptotic signals

Seal, S, Hockenbery, DM, Spaulding, EY, Kiem, HP, Abbassi, N, Deeg, HJ

Exp. Hematol. 2008
12887920 Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes

Micheau, O, Tschopp, J

Cell 2003
Participant Of
Orthologous Events