TRIF(TICAM1)-mediated TLR4 signaling

Stable Identifier
Homo sapiens
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TRIF (TICAM1) was shown to induce IRF3/7 and NF-kappa-B activation as well as apoptosis through distinct intracellular signaling pathways (Yamamoto M et al., 2003; Fitzgerald KA et al., 2003; Han KJ et al., 2004; Kaiser WJ & Offermann MK 2005).

TRIF consists of an N-terminal domain (NTD) (1-153), an intermediate disordered proline-rich region, a TIR domain, and a C-terminal region (Mahita J & Sowdhamin R 2017). The disordered proline-rich region between NTD domain and the TIR domain of TICAM1 contains binding sites for TRAF (TNF receptor associated factor) family proteins, which, in turn, recruit protein kinases to promote activation of IRF3 and/or NF-kappa-B (Sato S et al., 2003; Fitzgerald KA et al., 2003). The C-terminal region of TICAM1 (TRIF) can recruit receptor-interacting serine/threonine-protein kinase 1 (RIPK1), and this event is followed by the activation of the IKK complex or the induction of programmed cell death (Han KJ et al., 2004; Kaiser WJ & Offermann MK 2005).

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
12855817 Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway

Sugiyama, M, Takeuchi, O, Sanjo, H, Hoshino, K, Takeda, K, Okabe, M, Sato, S, Yamamoto, M, Kaisho, T, Hemmi, H

Science 2003
14739303 Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways

Zhang, J, Shu, HB, Han, KJ, Bin, LH, Su, X, Xu, LG

J. Biol. Chem. 2004
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Orthologous Events
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