Research
| Title： | SIRT5 impairs aggregation and activation of the signaling adaptor MAVS through catalyzing lysine desuccinylation |
|---|---|
| First author： | Liu, Xing; Zhu, Chunchun; Zha, Huangyuan; Tang, Jinhua; Rong, Fangjing; Chen, Xiaoyun; Fan, Sijia; Xu, Chenxi; Du, Juan; Zhu, Junji; Wang, Jing; Ouyang, Gang; Yu, Guangqing; Cai, Xiaolian; Chen, Zhu; Xiao, Wuhan |
| Journal： | EMBO JOURNAL |
| Years： | 2020 |
| DOI： | 10.15252/embj.2019103285 |
| Abstract： | RLR-mediated type I IFN production plays a pivotal role in innate antiviral immune responses, where the signaling adaptor MAVS is a critical determinant. Here, we show that MAVS is a physiological substrate of SIRT5. Moreover, MAVS is succinylated upon viral challenge, and SIRT5 catalyzes desuccinylation of MAVS. Mass spectrometric analysis indicated that Lysine 7 of MAVS is succinylated. SIRT5-catalyzed desuccinylation of MAVS at Lysine 7 diminishes the formation of MAVS aggregation after viral infection, resulting in the inhibition of MAVS activation and leading to the impairment of type I IFN production and antiviral gene expression. However, the enzyme-deficient mutant of SIRT5 (SIRT5-H158Y) loses its suppressive role on MAVS activation. Furthermore, we show that Sirt5-deficient mice are resistant to viral infection. Our study reveals the critical role of SIRT5 in limiting RLR signaling through desuccinylating MAVS. |
