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).
Kishida, S, Shibuya, H, Takaesu, G, Ninomiya-Tsuji, J, Matsumoto, K, Yamaguchi, K, Hiyama, A, Irie, K
Adhikari, A, Zeng, W, Chen, ZJ, Pineda, G, Sun, L, Chen, X, Jiang, X, Xia, ZP
Deng, L, Seth, RB, Kanayama, A, Shaito, A, Hong, M, Chiu, YH, Chen, ZJ, Sun, L, Ea, CK
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