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

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 modu...

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Bibliographic Details
Published in:PLoS pathogens 2017-03, Vol.13 (3), p.e1006264-e1006264
Main Authors: Wang, Qiang, Huang, Liyuan, Hong, Ze, Lv, Zhongshi, Mao, Zhaomin, Tang, Yijun, Kong, Xiufang, Li, Senlin, Cui, Ye, Liu, Heng, Zhang, Lele, Zhang, Xiaojie, Jiang, Lindi, Wang, Chen, Zhou, Qin
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biochemistry
Biology
Biology and life sciences
Cells, Cultured
Cellular signal transduction
Chronic conditions
College students
Deoxyribonucleic acid
DNA
Ectopic expression
Education
Enzymatic activity
Enzymes
Female
Gene expression
Genetic aspects
Health aspects
Herpes Simplex - immunology
Herpesvirus 1, Human
Herpesvirus infections
Hospitals
Humans
Immune response
Immune system
Immunity, Innate - immunology
Immunoblotting
Immunology
Immunoprecipitation
Innate immunity
Interferon
Kinases
Laboratories
Life sciences
Lupus
Lupus Erythematosus, Systemic - immunology
Male
Medicine
Medicine and Health Sciences
Microscopy, Confocal
Middle Aged
Mitochondrial Proteins - immunology
Nephrology
Nucleotidyltransferases - immunology
Proteins
Real-Time Polymerase Chain Reaction
Research and Analysis Methods
Rheumatology
RNA, Small Interfering
Stimulators
Systemic lupus erythematosus
Training
Transfection
Ubiquitin
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - immunology
Young Adult
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1006264