Activated TLR3:TRIF:K63pUb-TRAF6 recruits TAK1complex

Stable Identifier
R-HSA-177690
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Rotavirus, Influenza A virus, Hepatitis B virus, Hepatitis C Virus, Human herpesvirus 1
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TAK1-binding protein 2 (TAB2) and/or TAB3, as part of a complex that also contains TAK1 and TAB1, binds polyubiquitinated TRAF6. The TAB2 and TAB3 regulatory subunits of the TAK1 complex contain C-terminal Npl4 zinc finger (NZF) motifs that recognize with Lys63-pUb chains (Kanayama et al. 2004). The recognition mechanism is specific for Lys63-linked ubiquitin chains [Kulathu Y et al 2009]. TAK1 can be activated by unattached Lys63-polyubiquitinated chains when TRAF6 has no detectable polyubiquitination (Xia et al. 2009) and thus the synthesis of these chains by TRAF6 may be the signal transduction mechanism.This binding leads to autophosphorylation and activation of TAK1.

Literature References
PubMed ID Title Journal Year
17496917 Ubiquitin-mediated activation of TAK1 and IKK

Adhikari, A, Xu, M, Chen, ZJ

Oncogene 2007
12609980 Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR

Jiang, Z, Zamanian-Daryoush, M, Nie, H, Silva, AM, Williams, BR, Li, X

J Biol Chem 2003
19675569 Direct activation of protein kinases by unanchored polyubiquitin chains

Xia, ZP, Sun, L, Chen, X, Pineda, G, Jiang, X, Adhikari, A, Zeng, W, Chen, ZJ

Nature 2009
15327770 TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains

Kanayama, A, Seth, RB, Sun, L, Ea, CK, Hong, M, Shaito, A, Chiu, YH, Deng, L, Chen, ZJ

Mol Cell 2004
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