The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response

PLoS Pathogens

Chen Wang¹  Senlin Li¹  Lindi Jiang¹  Zhaomin Mao²  Ze Hong²  Yijun Tang²  Qiang Wang²  Zhongshi Lv³  Qin Zhou⁴  Heng Liu⁴  Xiufang Kong⁴  Liyuan Huang⁴  Ye Cui⁴  Xiaojie Zhang⁴  Lele Zhang⁴ 

[1] Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China;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;School of Life Science and Technology, China Pharmaceutical University, Jiangning District, Nanjing, China;State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

关键词: Small interfering RNAs;    L929 cells;    Immunoprecipitation;    Transfection;    Ubiquitination;    Systemic lupus erythematosus;    Phosphorylation;    Ubiquitin ligases;   

DOI  :  10.1371/journal.ppat.1006264

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

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