HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor   Signaling Pathway by Inhibiting TRAF3 Ubiquitination via Recruiting   OTUB1

doi:10.1371/journal.ppat.1004041

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	HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination via Recruiting OTUB1
	Peng, Yanyan ; Xu, Ruidan ; Zheng, Xiaofeng
刊名	plos pathogens
	2014
关键词	PATTERN-RECOGNITION RECEPTORS NF-KAPPA-B ADAPTER PROTEIN IKK-EPSILON VIRUS ROLES INDUCTION GENE IRF3 DEUBIQUITINATION
DOI	10.1371/journal.ppat.1004041
英文摘要	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-kappa B. Here we demonstrated that HSCARG participates in innate immunity. HSCARG inhibited the cellular antiviral response in an NF-kappa B 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 (IKK epsilon) after viral infection and impaired the association between TRAF3 and IKK epsilon, which further decreased the phosphorylation of IKK epsilon 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-beta 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.; Microbiology; Parasitology; Virology; SCI(E); PubMed; 3; ARTICLE; xiaofengz@pku.edu.cn; 4; e1004041; 10
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/189477]
专题	生命科学学院
推荐引用方式 GB/T 7714	Peng, Yanyan,Xu, Ruidan,Zheng, Xiaofeng. HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination via Recruiting OTUB1[J]. plos pathogens,2014.
APA	Peng, Yanyan,Xu, Ruidan,&Zheng, Xiaofeng.(2014).HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination via Recruiting OTUB1.plos pathogens.
MLA	Peng, Yanyan,et al."HSCARG Negatively Regulates the Cellular Antiviral RIG-I Like Receptor Signaling Pathway by Inhibiting TRAF3 Ubiquitination via Recruiting OTUB1".plos pathogens (2014).