Recruitment of TAK1 kinase complex to oligo-K63-pUb-TRAF6

Stable Identifier
Reaction [binding]
Homo sapiens
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K-63 linked polyubiquitin (pUb) chain on TRAF6 provides a scaffold to recruit downstream effector molecules to activate NF-kB. Transforming growth factor beta-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase (MAPK) kinase kinase family is shown to be an essential intermediate that transmits the upstream signals from the receptor complex to the downstream MAPKs and to the NF-kB pathway (Broglie et al. 2009). TAK1-binding protein 1 (TAB1), TAB2 and TAB3 constitutively bound to TAK1. TAB1 acts as the activation subunit of the TAK1 complex, aiding in the autophosphorylation of TAK1, whereas TAB2 and its homologue TAB3, act as a adaptors of TAK1 that facilitate the assembly of TAK1 complex to TRAF6. The highly conserved C-terminal zinc finger domain of TAB2 and TAB3 binds preferentially to the K-63-linked polyubiquitin chains on TRAF6 (Broglie et al. 2009, Besse et al. 2007).
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
17158449 TAK1-dependent signaling requires functional interaction with TAB2/TAB3

Maddineni, U, Wu, H, Darnay, BG, Lin, SC, Besse, A, Lamothe, B, Campos, AD, Webster, WK

J Biol Chem 2007
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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