Activated TRAF6:p-IRAK2 interacts with TAK1 complex

Stable Identifier
R-HSA-936960
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
ReviewStatus
5/5
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Activated TRAF6:p-IRAK2 interacts with TAK1 complex
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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
19935683 Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain

Bremm, A, Kulathu, Y, Hofmann, K, Komander, D, Akutsu, M

Nat. Struct. Mol. Biol. 2009
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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Orthologous Events
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Activated TRAF6:p-IRAK2 interacts with TAK1 complex (Mus musculus)
Activated TRAF6:p-IRAK2 interacts with TAK1 complex (Rattus norvegicus)
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pUb_TRAF6 pIRAK2 recruits TAK1 kinase complex (Gallus gallus)
Authored
Shamovsky, V  (2010-06-01)
Reviewed
Gillespie, ME  (2010-11-30)
Napetschnig, J  (2012-11-16)
Created
Shamovsky, V  (2010-08-25)
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