Phosphorylation of Ser82 on IRF3 acts as negative-feedback regulation of IRF3-dependent innate immunity

Qi Cheng; Lijia Yuan; Junhui Guo; Deyin Guo; Xueyan Liu; Shun Li

doi:10.1016/j.biocel.2022.106275

Phosphorylation of Ser82 on IRF3 acts as negative-feedback regulation of IRF3-dependent innate immunity

Int J Biochem Cell Biol. 2022 Sep:150:106275. doi: 10.1016/j.biocel.2022.106275. Epub 2022 Aug 7.

Authors

Qi Cheng¹, Lijia Yuan², Junhui Guo¹, Deyin Guo³, Xueyan Liu⁴, Shun Li⁵

Affiliations

¹ College of Life Sciences, Wuhan University of Technologies, Wuhan, Hubei, China.
² Department of Critical Care Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medicine College of Jinan University, Shenzhen, China.
³ Institute of Precision Medicine, The First Affiliated Hospital, School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
⁴ Department of Critical Care Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medicine College of Jinan University, Shenzhen, China. Electronic address: 13554843721@163.com.
⁵ CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China. Electronic address: shun.li@siat.ac.cn.

PMID: 35948267
DOI: 10.1016/j.biocel.2022.106275

Abstract

Interferon Regulatory Factor 3 (IRF3) is essential for the production of type I interferon (IFN) during virus infection; however, the mechanism underlying its regulation remains to be elucidated. Here we have identified a novel negative regulatory phosphorylation site on IRF3. In this study, we discovered that Ser82 phosphorylation on IRF3 abrogates virus-induced IFN-β activation. Furthermore, our results clarified the mechanism in which Ser82 phosphorylation on IRF3 retains the function of dimerization and nuclear import, but abolishes the promoter binding ability of IRF3. In addition, Ser82 phosphorylation on IRF3 serves as a negative feedback mechanism for the type I IFN response. These findings elucidate a previously unknown mechanism for negatively regulating IRF3 to finely tune type I IFN response.

Keywords: IRF3; Innate immunity; Negative regulation phosphorylation site; Promoter DNA binding; Type I interferon.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Feedback
Immunity, Innate
Interferon Regulatory Factor-3*
Phosphorylation
Protein Serine-Threonine Kinases*
Signal Transduction

Substances

Interferon Regulatory Factor-3
Protein Serine-Threonine Kinases