Open AccessThe E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response
Author(s) -
Qiang Wang,
Liyuan Huang,
Ze Hong,
Zhongshi Lv,
Zhizhong Mao,
Yijun Tang,
Xiangzhen Kong,
Senlin Li,
Ye Cui,
Heng Liu,
Lele Zhang,
Xiaojie Zhang,
Lindi Jiang,
Chen Wang,
Qin Zhou
Publication year - 2017
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1006264
Subject(s) - ubiquitin ligase , irf3 , innate immune system , ubiquitin , gene knockdown , ectopic expression , microbiology and biotechnology , dna ligase , interferon , biology , signal transduction , chemistry , immune system , enzyme , gene , biochemistry , immunology
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.