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SIRT5 impairs aggregation and activation of the signaling adaptor MAVS through catalyzing lysine desuccinylation
Liu, Xing1; Zhu, Chunchun1,2; Zha, Huangyuan1; Tang, Jinhua1,2; Rong, Fangjing1,2; Chen, Xiaoyun1,2; Fan, Sijia1,2; Xu, Chenxi1; Du, Juan1; Zhu, Junji1,2; Wang, Jing1; Ouyang, Gang1; Yu, Guangqing1,2; Cai, Xiaolian1; Chen, Zhu1; Xiao, Wuhan1,2,3,4,5
2020-04-17
Source PublicationEMBO JOURNAL
ISSN0261-4189
Issue1Pages:18
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.

Keyworddesuccinylation innate immunity MAVS SIRT5 viral infection
DOI10.15252/embj.2019103285
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000526135000001
WOS KeywordRIG-I ; PROTEIN ; SUCCINATE ; SUCCINYLATION ; IDENTIFICATION ; MALONYLATION ; MACROPHAGES ; DEAMIDATION ; RECOGNITION ; IL-1-BETA
PublisherWILEY
Citation statistics
Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/36058
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorXiao, Wuhan
Affiliation1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Minist Agr, Key Lab Aquaculture Dis Control, Wuhan, Peoples R China
4.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan, Peoples R China
5.Chinese Acad Sci, Innovat Acad Seed Design, Wuhan, Peoples R China
Recommended Citation
GB/T 7714
Liu, Xing,Zhu, Chunchun,Zha, Huangyuan,et al. SIRT5 impairs aggregation and activation of the signaling adaptor MAVS through catalyzing lysine desuccinylation[J]. EMBO JOURNAL,2020(1):18.
APA Liu, Xing.,Zhu, Chunchun.,Zha, Huangyuan.,Tang, Jinhua.,Rong, Fangjing.,...&Xiao, Wuhan.(2020).SIRT5 impairs aggregation and activation of the signaling adaptor MAVS through catalyzing lysine desuccinylation.EMBO JOURNAL(1),18.
MLA Liu, Xing,et al."SIRT5 impairs aggregation and activation of the signaling adaptor MAVS through catalyzing lysine desuccinylation".EMBO JOURNAL .1(2020):18.
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