E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1
G Song, B Liu, Z Li, H Wu, P Wang, K Zhao… - Nature …, 2016 - nature.com
G Song, B Liu, Z Li, H Wu, P Wang, K Zhao, G Jiang, L Zhang, C Gao
Nature immunology, 2016•nature.comTBK1 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 …
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 …
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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