The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response Qiang Wang Liyuan Huang Ze Hong Zhongshi Lv Zhaomin Mao Yijun Tang Xiufang Kong Senlin Li Ye Cui Heng Liu Lele Zhang Xiaojie Zhang Lindi Jiang Chen Wang Qin Zhou 10.1371/journal.ppat.1006264 https://plos.figshare.com/articles/dataset/The_E3_ubiquitin_ligase_RNF185_facilitates_the_cGAS-mediated_innate_immune_response/4736107 <div><p>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.</p></div> 2017-03-08 18:53:02 Systemic Lupus Erythematosus K 27-linked poly-ubiquitination IRF 3-responsive gene expression study uncovers RNF 185 STING E 3 ubiquitin ligase RNF 185 HSV E 3 ubiquitin ligase ER ubiquitin ligase RNF 185 interacted RNF 185 SLE cyclic GMP-AMP synthase RNF 185 mRNA cytosolic DNA stimulation cGAS