TRAF3 binds to TRIF:activated TLR3 complex

Stable Identifier
R-HSA-9013992
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Rotavirus, Influenza A virus, Hepatitis B virus, Hepatitis C Virus, Human herpesvirus 1
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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

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

Nature 2006
19898473 Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines

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

Nat Immunol 2010
16306937 Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6

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

Nature 2006
Participants
Participant Of
Authored
Reviewed
Created