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.
Keyphrases
- immune response
- systemic lupus erythematosus
- gene expression
- dendritic cells
- dna damage response
- poor prognosis
- end stage renal disease
- toll like receptor
- hydrogen peroxide
- chronic kidney disease
- disease activity
- dna methylation
- binding protein
- ejection fraction
- escherichia coli
- genome wide
- drug delivery
- rheumatoid arthritis
- prognostic factors
- oxidative stress
- peritoneal dialysis
- long non coding rna
- protein kinase
- cancer therapy
- pseudomonas aeruginosa
- patient reported