E3泛素连接酶RNF185促进cGAS介导的先天性免疫反应。
The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response.
作者信息
Wang Qiang, Huang Liyuan, Hong Ze, Lv Zhongshi, Mao Zhaomin, Tang Yijun, Kong Xiufang, Li Senlin, Cui Ye, Liu Heng, Zhang Lele, Zhang Xiaojie, Jiang Lindi, Wang Chen, Zhou Qin
机构信息
Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
出版信息
PLoS Pathog. 2017 Mar 8;13(3):e1006264. doi: 10.1371/journal.ppat.1006264. eCollection 2017 Mar.
The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2'3'-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dynamically. Here, we reported that the ER ubiquitin ligase RNF185 interacted with cGAS during HSV-1 infection. Ectopic-expression or knockdown of RNF185 respectively enhanced or impaired the IRF3-responsive gene expression. Mechanistically, RNF185 specifically catalyzed the K27-linked poly-ubiquitination of cGAS, which promoted its enzymatic activity. Additionally, Systemic Lupus Erythematosus (SLE) patients displayed elevated expression of RNF185 mRNA. Collectively, this study uncovers RNF185 as the first E3 ubiquitin ligase of cGAS, shedding light on the regulation of cGAS activity in innate immune responses.
环磷酸鸟苷-腺苷酸合成酶（cGAS）在胞质DNA刺激下，催化第二信使2'3'-cGAMP的形成，后者随后与干扰素基因刺激因子（STING）结合并激活下游信号传导。cGAS酶活性如何动态调节仍有待阐明。在此，我们报道内质网泛素连接酶RNF185在单纯疱疹病毒1型（HSV-1）感染期间与cGAS相互作用。RNF185的异位表达或敲低分别增强或损害IRF3反应性基因的表达。机制上，RNF185特异性催化cGAS的K27连接的多聚泛素化，从而促进其酶活性。此外，系统性红斑狼疮（SLE）患者的RNF185 mRNA表达升高。总之，本研究揭示RNF185是cGAS的首个E3泛素连接酶，为先天免疫反应中cGAS活性的调节提供了线索。
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