Reactome | TRAF3 binds TICAM1:activated TLR4 complex

TRAF3 binds TICAM1:activated TLR4 complex

Stable Identifier

R-HSA-2201338

Type

Reaction [binding]

Species

Homo sapiens

Compartment

endosome membrane, cytosol

Synonyms

TRAF3 binds TRIF:activated TLR4 complex, TRAF3 binds TICAM1:TRAM:TLR4:LY96:LPS:CD14

ReviewStatus

5/5

Locations in the PathwayBrowser

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Immune System (Homo sapiens)

- Innate Immune System (Homo sapiens)
  - Toll-like Receptor Cascades (Homo sapiens)
    - Toll Like Receptor 4 (TLR4) Cascade (Homo sapiens)
      - MyD88-independent TLR4 cascade (Homo sapiens)
        
        TRIF (TICAM1)-mediated TLR4 signaling (Homo sapiens)
        
        Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) (Homo sapiens)
        
        TRAF3 binds TICAM1:activated TLR4 complex (Homo sapiens)

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TRAF3 binds TICAM1:activated TLR4 complex

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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 Tseng, PH, Matsuzawa, A, Zhang, W, Mino, T, Vignali, DA, Karin, M	Nat Immunol	2010
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
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