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

Cheng, Qi1; Yuan, Lijia2; Guo, Junhui1; Guo, Deyin3; Liu, Xueyan2; Li, Shun4

2022-09-01

10.1016/j.biocel.2022.106275

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY   Impact Factor & Quartile

1357-2725

1878-5875

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-8 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.

Type I interferon IRF3 Negative regulation phosphorylation site Promoter DNA binding Innate immunity

SCI

English

Corresponding

Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections[ZDSYS20200811142804014] ; Shenzhen Key Medical Discipline Construction Fund[SZXK045]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000854908300003

PERGAMON-ELSEVIER SCIENCE LTD

Web of Science

1.Wuhan Univ Technol, Coll Life Sci, Wuhan, Hubei, Peoples R China
2.Jinan Univ, Dept Crit Care Med, Shenzhen Peoples Hosp, Affiliated Hosp 1,Southern Univ Sci & Technol,Clin, Shenzhen, Peoples R China
3.Sun Yat sen Univ, Affiliated Hosp 1, Inst Precis Med, Sch Med, Guangzhou, Guangdong, Peoples R China
4.Chinese Acad Sci, CAS Key Lab Quantitat Engn Biol, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Shenzhen 518055, Peoples R China

Cheng, Qi,Yuan, Lijia,Guo, Junhui,et al. Phosphorylation of Ser82 on IRF3 acts as negative-feedback regulation of IRF3-dependent innate immunity[J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2022,150.

Cheng, Qi,Yuan, Lijia,Guo, Junhui,Guo, Deyin,Liu, Xueyan,&Li, Shun.(2022).Phosphorylation of Ser82 on IRF3 acts as negative-feedback regulation of IRF3-dependent innate immunity.INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,150.

Cheng, Qi,et al."Phosphorylation of Ser82 on IRF3 acts as negative-feedback regulation of IRF3-dependent innate immunity".INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 150(2022).