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Ubiquitin E3 ligase MID1 inhibits the innate immune response by ubiquitinating IRF3
Author(s) -
Chen Xiangjie,
Xu Ying,
Tu Wenhui,
Huang Fan,
Zuo Yibo,
Zhang HongGuang,
Jin Lincong,
Feng Qian,
Ren Tengfei,
He Jiuyi,
Miao Ying,
Yuan Yukang,
Zhao Qian,
Liu Jiapeng,
Zhang Renxia,
Zhu Li,
Qian Feng,
Zhu Chuanwu,
Zheng Hui,
Wang Jun
Publication year - 2021
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13315
Subject(s) - irf3 , ubiquitin ligase , ubiquitin , interferon regulatory factors , innate immune system , microbiology and biotechnology , biology , interferon , transcription factor , immune system , immunology , biochemistry , gene
Summary Interferon regulatory factor 3 (IRF3) is a critical transcription factor for inducing production of type I interferons (IFN‐I) and regulating host antiviral response. Although IRF3 activation during viral infection has been extensively studied, the inhibitory regulation of IRF3 remains largely unexplored. Here, we revealed that Midline‐1 (MID1) is a ubiquitin E3 ligase of IRF3 that plays essential roles in regulating the production of IFN‐I. We found that MID1 physically interacts with IRF3 and downregulates IRF3 protein levels. Next, we demonstrated that MID1 can induce K48‐linked polyubiquitination of IRF3, thus lowing the protein stability of IRF3. Our further studies identified Lys313 as a major ubiquitin acceptor lysine of IRF3 induced by MID1. Finally, MID1‐mediated ubiquitination and degradation of IRF3 restrict IFN‐I production and cellular antiviral response. This study uncovers a role of MID1 in regulating innate antiviral immunity and may provide a potential target for enhancing host antiviral activity.