TRAF3 binds TICAM1:activated TLR4 complex

Stable Identifier
Reaction [binding]
Homo sapiens
TRAF3 binds TRIF:activated TLR4 complex, TRAF3 binds TICAM1:TRAM:TLR4:LY96:LPS:CD14
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Tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3) is a ubiquitin ligase recruited to both MYD88- and TRIF-assembled signalling complexes (Hacker H et al., 2006). However, TRAF3 controls the production of interferon and proinflammatory cytokines in different ways (Tseng PH et al., 2010). Positive or negative type of regulation is dictated by TRAF3 subcellular distribution and its mode of ubiquitination. Thus, TRIF-mediated signaling initiated on endosomes triggers TRAF3 self-ubiquitination through noncanonical (K63-linked) polyubiquitination, which is essential for activation of IRF3/7 and the interferon response. In contrast, during MyD88-dependent signaling initiated from plasma membrane TRAF3 functions as a negative regulator of inflammatory cytokines and mitogen-activated protein kinases (MAPKs), unless it undergoes degradative (K48-linked) polyubiquitination mediated by TRAF6 and a pair of the ubiquitin ligases cIAP1 and cIAP2. The degradation of TRAF3 is essential for MAPK activation via TAK1 and MEKK1 (Tseng PH et al., 2010).
Literature References
PubMed ID Title Journal Year
19898473 Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines

Mino, T, Matsuzawa, A, Karin, M, Zhang, W, Tseng, PH, Vignali, DA

Nat Immunol 2010
16306936 Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response

Perry, A, Saha, SK, Oganesyan, G, He, JQ, Guo, B, Shahangian, A, Cheng, G, Zarnegar, B

Nature 2006
16306937 Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6

Hsu, LC, Raz, E, Häcker, G, Karin, M, Kamps, MP, Mann, M, Kratchmarova, I, Redecke, V, Blagoev, B, Häcker, H, Wagner, H, Wang, GG

Nature 2006
This event is regulated
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