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