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. 2016 Dec;17(12):1342-1351.
doi: 10.1038/ni.3588. Epub 2016 Oct 24.

E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1

Guanhua Song  1   2 , Bingyu Liu  1 , Zhihui Li  2 , Haifeng Wu  1 , Peng Wang  1 , Kai Zhao  1 , Guosheng Jiang  2 , Lei Zhang  1 , Chengjiang Gao  1
Affiliations

E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1

Guanhua Song et al. Nat Immunol. 2016 Dec.

Abstract

TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, IRF3 activation and IFN-β production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-β production and innate antiviral immune responses to RNA and DNA viruses, in vitro and in vivo. Our study identified RNF128 as an E3 ligase for K63-linked ubiquitination and activation of TBK1 and delineated a previously unrecognized function for RNF128.

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