RIP3 binds TRIF to mediate necroptosis

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Reaction [transition]
Homo sapiens
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TLR3 and TLR4 -directed programmed necrosis (necroptosis) is mediated by the TRIF-RIP3 pathway in mouse macrophages [He S e al 2011]. RIP3 was shown to be essential mediator in TLR3-induced necroptotic cell death in human epithelial cell lines. Knockdown of RIP3 in human keratinocyte HaCaT cells blocked TLR3-mediated necroptosis without affecting the apoptotic response. Moreover, overexpression of RIP3 in human epithelial carcinoma cell line HeLa led to increased caspase-independent TLR3-induced cell death in the absence of IAPs [Feoktistova M et al 2011]. In addition, in caspase-8- or FADD-deficient human Jurkat cells dsRNA induced programmed necrosis, instead of apoptosis [Kalai M et al 2002]. Thus, when caspase-dependent apoptosis is inhibited or absent, the alternative RIP3-mediated programmed cell death is induced.
Literature References
PubMed ID Title Journal Year
15814722 Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif

Offermann, MK, Kaiser, WJ

J Immunol 2005
22123964 Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway

Wang, X, Liang, Y, Shao, F, He, S

Proc. Natl. Acad. Sci. U.S.A. 2011
12181749 Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA

Kalai, M, Van Loo, G, Vandenabeele, P, Burm, W, Meeus, A, Vanden Berghe, T, Saelens, X

Cell Death Differ. 2002
21737330 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms

Langlais, C, Geserick, P, Kellert, B, H├Ącker, G, Cain, K, Feoktistova, M, Hupe, M, MacFarlane, M, Leverkus, M, Dimitrova, DP

Mol. Cell 2011
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