RESEARCH ARTICLE

Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1

  • Jie-lin Tang 1,2 ,
  • Qi Yang 1 ,
  • Chong-hui Xu 1,2 ,
  • He Zhao 1 ,
  • Ya-ling Liu 1,2 ,
  • Can-yu Liu 1,2 ,
  • Yuan Zhou 1 ,
  • Dong-wei Gai 1,2 ,
  • Rong-juan Pei 1 ,
  • Yun Wang 1 ,
  • Xue Hu 1 ,
  • Bo Zhong 3 ,
  • Yan-yi Wang 1 ,
  • Xin-wen Chen , 1,4 ,
  • Ji-zheng Chen , 1
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  • 1. State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
  • 2. University of Chinese Academy of Sciences, Beijing 100049, China
  • 3. Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China
  • 4. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China

Received date: 12 Apr 2020

Accepted date: 17 Jun 2020

Published date: 15 Apr 2021

Copyright

2020 The Author(s)

Abstract

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

Cite this article

Jie-lin Tang , Qi Yang , Chong-hui Xu , He Zhao , Ya-ling Liu , Can-yu Liu , Yuan Zhou , Dong-wei Gai , Rong-juan Pei , Yun Wang , Xue Hu , Bo Zhong , Yan-yi Wang , Xin-wen Chen , Ji-zheng Chen . Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1[J]. Protein & Cell, 2021 , 12(4) : 261 -278 . DOI: 10.1007/s13238-020-00751-5

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