PLoS Pathogens | |
HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination via Recruiting OTUB1 | |
Ruidan Xu1  Yanyan Peng2  Xiaofeng Zheng2  | |
[1] Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing, China;State Key Lab of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China | |
关键词: Ubiquitination; Transcription factors; Interferons; Phosphorylation; Luciferase assay; Viral transmission; infection; Small interfering RNAs; Vesicular stomatitis virus; | |
DOI : 10.1371/journal.ppat.1004041 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
RIG-I like receptors (RLRs) recognize cytosolic viral RNA and initiate innate immunity; they increase the production of type I interferon (IFN) and the transcription of a series of antiviral genes to protect the host organism. Accurate regulation of the RLR pathway is important for avoiding tissue injury induced by excessive immune response. HSCARG is a newly reported negative regulator of NF-κB. Here we demonstrated that HSCARG participates in innate immunity. HSCARG inhibited the cellular antiviral response in an NF-κB independent manner, whereas deficiency of HSCARG had an opposite effect. After viral infection, HSCARG interacted with tumor necrosis receptor-associated factor 3 (TRAF3) and inhibited its ubiquitination by promoting the recruitment of OTUB1 to TRAF3. Knockout of HSCARG attenuated the de-ubiquitination of TRAF3 by OTUB1, and knockdown of OTUB1 abolished the effect of HSCARG. HSCARG also interacted with Ikappa-B kinase epsilon (IKKε) after viral infection and impaired the association between TRAF3 and IKKε, which further decreased the phosphorylation of IKKε and interferon response factor 3 (IRF3), thus suppressed the dimerization and nuclear translocation of IRF3. Moreover, knockdown of TRAF3 dampened the inhibitory effect of IFN-β transcription by HSCARG, suggesting that TRAF3 is necessary for HSCARG to down-regulate RLR pathway. This study demonstrated that HSCARG is a negative regulator that enables balanced antiviral innate immunity.
【 授权许可】
CC BY
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