2. Academic Validation
  3. The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response

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

  • PLoS Pathog. 2017 Mar 8;13(3):e1006264. doi: 10.1371/journal.ppat.1006264.
Qiang Wang 1 2,  Liyuan Huang 1,  Ze Hong 3,  Zhongshi Lv 1,  Zhaomin Mao 1,  Yijun Tang 2,  Xiufang Kong 4,  Senlin Li 2,  Ye Cui 2,  Heng Liu 2,  Lele Zhang 2,  Xiaojie Zhang 4,  Lindi Jiang 4,  Chen Wang 2 3,  Qin Zhou 1
Affiliations

Affiliations

  • 1 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.
  • 2 State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 3 School of Life Science and Technology, China Pharmaceutical University, Jiangning District, Nanjing, China.
  • 4 Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.
PMID: 28273161 DOI: 10.1371/journal.ppat.1006264
Abstract

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.

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