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SIRT5 impairs aggregation and activation of the signaling adaptor MAVS through catalyzing lysine desuccinylation
- Source :
- EMBO J
- Publication Year :
- 2020
- Publisher :
- EMBO, 2020.
-
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.
- Subjects :
- SIRT5
Mutant
Lysine
Mutation, Missense
Biology
Viral infection
General Biochemistry, Genetics and Molecular Biology
Mice
Protein Aggregates
03 medical and health sciences
0302 clinical medicine
Immune system
Animals
Humans
Sirtuins
Molecular Biology
Adaptor Proteins, Signal Transducing
030304 developmental biology
Mice, Knockout
0303 health sciences
Innate immune system
General Immunology and Microbiology
General Neuroscience
Type I IFN production
Articles
HCT116 Cells
Cell biology
Antiviral gene
HEK293 Cells
Amino Acid Substitution
Gene Expression Regulation
Interferon Type I
bacteria
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14602075 and 02614189
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- The EMBO Journal
- Accession number :
- edsair.doi.dedup.....baab01c9c0806dca4cbbcb3a0681763d