泛素连接酶
泛素
信号转导衔接蛋白
粒体自噬
信号转导
自噬
生物化学
作者
Xing Liu,Chunchun Zhu,Huangyuan Zha,Jinhua Tang,Fangjing Rong,Xiaoyun Chen,Sijia Fan,Chenxi Xu,Juan Du,Junji Zhu,Jing Wang,Gang Ouyang,Guangqing Yu,Xiaolian Cai,Zhu Chen,Wuhan Xiao
标识
DOI:10.15252/embj.2019103285
摘要
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.
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