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  • Acetylation-Dependent Deubiquitinase OTUD3 Controls MAVS Activation in Innate Antiviral Immunity.

Acetylation-Dependent Deubiquitinase OTUD3 Controls MAVS Activation in Innate Antiviral Immunity.

Molecular cell (2020-07-18)
Zhengkui Zhang, Xiuwu Fang, Xiaojin Wu, Li Ling, Feng Chu, Jingxian Li, Shuai Wang, Jia Zang, Bo Zhang, Sheng Ye, Long Zhang, Bing Yang, Shixian Lin, Huizhe Huang, Aijun Wang, Fangfang Zhou
ZUSAMMENFASSUNG

Accurate regulation of innate immunity is necessary for the host to efficiently respond to invading pathogens and avoid excessive harmful immune pathology. Here we identified OTUD3 as an acetylation-dependent deubiquitinase that restricts innate antiviral immune signaling. OTUD3 deficiency in mice results in enhanced innate immunity, a diminished viral load, and morbidity. OTUD3 directly hydrolyzes lysine 63 (Lys63)-linked polyubiquitination of MAVS and thus shuts off innate antiviral immune response. Notably, the catalytic activity of OTUD3 relies on acetylation of its Lys129 residue. In response to virus infection, the acetylated Lys129 is removed by SIRT1, which promptly inactivates OTUD3 and thus allows timely induction of innate antiviral immunity. Importantly, acetyl-OTUD3 levels are inversely correlated with IFN-β expression in influenza patients. These findings establish OTUD3 as a repressor of MAVS and uncover a previously unknown regulatory mechanism by which the catalytic activity of OTUD3 is tightly controlled to ensure timely activation of antiviral defense.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Millipore
ANTI-FLAG® M2-Affinitätsgel, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Monoklonaler ANTI-FLAG® M2-Antikörper in Maus hergestellte Antikörper, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
Nicotinamid, ≥99.5% (HPLC)
Sigma-Aldrich
N-Ethylmaleimid, crystalline, ≥98% (HPLC)