USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA

文献类型： 外文期刊

第一作者： Zhang, Man

作者： Zhang, Man;Zhang, Meng-Xin;Zhang, Qiang;Zhu, Gao-Feng;Yuan, Lei;Yao, Jing;Zhong, Bo;Shu, Hong-Bing;Zhong, Bo;Zhu, Qiyun;Zhang, Dong-Er;Zhang, Dong-Er

作者机构：

关键词： USP18;USP20;STING/MITA;deubiquitination;innate antiviral response

期刊名称：CELL RESEARCH （ 影响因子：25.617； 五年影响因子：25.924 ）

ISSN： 1001-0602

年卷期： 2016 年 26 卷 12 期

页码：

收录情况： SCI

摘要： STING (also known as MITA) mediates the innate antiviral signaling and ubiquitination of STING is key to its function. However, the deubiquitination process of STING is unclear. Here we report that USP18 recruits USP20 to deconjugate K48-linked ubiquitination chains from STING and promotes the stability of STING and the expression of type I IFNs and proinflammatory cytokines after DNA virus infection. USP18 deficiency or knockdown of USP20 resulted in enhanced K48-linked ubiquitination and accelerated degradation of STING, and impaired activation of IRF3 and NF-kappa B as well as induction of downstream genes after infection with DNA virus HSV-1 or transfection of various DNA ligands. In addition, Usp18(-/-) mice were more susceptible to HSV-1 infection compared with the wildtype littermates. USP18 did not deubiquitinate STING in vitro but facilitated USP20 to catalyze deubiquitination of STING in a manner independent of the enzymatic activity of USP18. In addition, reconstitution of STING into Usp18(-/-) MEFs restored HSV-1-induced expression of downstream genes and cellular antiviral responses. Our findings thus uncover previously uncharacterized roles of USP18 and USP20 in mediating virus-triggered signaling and contribute to the understanding of the complicated regulatory system of the innate antiviral responses.

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