Activated TLR4:TICAM1:K63pUb-TRAF6 recruits TAK1complex

Stable Identifier
Reaction [binding]
Homo sapiens
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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.

As a de-ubiquitinating/de-ISGylating enzyme, severe acute respiratory syndrome coronavirus type 1 (SARS-CoV-1) 1a-encoded papain-like protease (PLPro or nsp3) antagonizes the host type I interferon (IFN) response by removing Lys63-linked ubiquitin chains of TRAF3 and TRAF6 (Li SW et al. 2016).

Literature References
PubMed ID Title Journal Year
10882101 TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway

Kishida, S, Shibuya, H, Takaesu, G, Ninomiya-Tsuji, J, Matsumoto, K, Yamaguchi, K, Hiyama, A, Irie, K

Mol Cell 2000
19675569 Direct activation of protein kinases by unanchored polyubiquitin chains

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

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

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

Mol Cell 2004
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