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  • Title: USP20 Promotes Cellular Antiviral Responses via Deconjugating K48-Linked Ubiquitination of MITA.
    Author: Zhang MX, Cai Z, Zhang M, Wang XM, Wang Y, Zhao F, Zhou J, Luo MH, Zhu Q, Xu Z, Zeng WB, Zhong B, Lin D.
    Journal: J Immunol; 2019 Apr 15; 202(8):2397-2406. PubMed ID: 30814308.
    Abstract:
    Mediator of IRF3 activation ([MITA] also known as STING) is a direct sensor of cyclic dinucleotide and critically mediates cytoplasmic DNA--triggered innate immune signaling. The activity of MITA is extensively regulated by ubiquitination and deubiquitination. In this study, we report that USP20 interacts with and removes K48-linked ubiquitin chains from MITA after HSV-1 infection, thereby stabilizing MITA and promoting cellular antiviral responses. Deletion of USP20 accelerates HSV-1-induced degradation of MITA and impairs phosphorylation of IRF3 and IκBα as well as subsequent induction of type I IFNs and proinflammatory cytokines after HSV-1 infection or cytoplasmic DNA challenge. Consistently, Usp20 -/- mice produce decreased type I IFNs and proinflammatory cytokines, exhibit increased susceptibility to lethal HSV-1 infection, and aggravated HSV-1 replication compared with Usp20 +/+ mice. In addition, complement of MITA into Usp20 -/- cells fully restores HSV-1-triggered signaling and inhibits HSV-1 infection. These findings suggest a crucial role of USP20 in maintaining the stability of MITA and promoting innate antiviral signaling.
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