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学科主题基础医学
Smurf2 Negatively Modulates RIG-I-Dependent Antiviral Response by Targeting VISA/MAVS for Ubiquitination and Degradation
Pan, Yu; Li, Rui; Meng, Jun-Ling; Mao, He-Ting; Zhang, Yu; Zhang, Jun
刊名JOURNAL OF IMMUNOLOGY
2014-05-15
DOI10.4049/jimmunol.1302632
192期:10页:4758-4764
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Immunology
研究领域[WOS]Immunology
关键词[WOS]NF-KAPPA-B ; ADAPTER PROTEIN ; MAVS ; RECEPTORS ; LIGASES ; RNA ; RECOGNITION ; RECRUITMENT ; ACTIVATION ; INDUCTION
英文摘要

VISA (also known as MAVS, Cardif, IPS-1) is the essential adaptor protein for virus-induced activation of IFN regulatory factors 3 and 7 and production of type I IFNs. Understanding the regulatory mechanisms for VISA will provide detailed insights into the positive or negative regulation of innate immune responses. In this study, we identified Smad ubiquitin regulatory factor (Smurf) 2, one of the Smad ubiquitin regulator factor proteins, as an important negative regulator of virus-triggered type I IFN signaling, which targets at the VISA level. Overexpression of Smurf2 inhibits virus-induced IFN-b and IFN-stimulated response element activation. The E3 ligase defective mutant Smurf2/C716A loses the ability to suppress virus-induced type I IFN signaling, suggesting that the negative regulation is dependent on the ubiquitin E3 ligase activity of Smurf2. Further studies demonstrated that Smurf2 interacted with VISA and targeted VISA for K48-linked ubiquitination, which promoted the degradation of VISA. Consistently, knockout or knockdown of Smurf2 expression therefore promoted antiviral signaling, which was correlated with the increase in protein stability of VISA. Our findings suggest that Smurf2 is an important nonredundant negative regulator of virus-triggered type I IFN signaling by targeting VISA for K48-linked ubiquitination and degradation.

语种英语
WOS记录号WOS:000335973600033
项目编号2011CB946103 ; 2010CB945300
资助机构National Basic Research Program of China ; Program for New Century Excellent Talents in University
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被引频次:28[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65222
专题北京大学基础医学院_免疫学系
北京大学第一临床医学院_手术室
作者单位Peking Univ, Key Lab Med Immunol, Sch Basic Med Sci, Dept Immunol,Minist Hlth,Hlth Sci Ctr, Beijing 100191, Peoples R China
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Pan, Yu,Li, Rui,Meng, Jun-Ling,et al. Smurf2 Negatively Modulates RIG-I-Dependent Antiviral Response by Targeting VISA/MAVS for Ubiquitination and Degradation[J]. JOURNAL OF IMMUNOLOGY,2014,192(10):4758-4764.
APA Pan, Yu,Li, Rui,Meng, Jun-Ling,Mao, He-Ting,Zhang, Yu,&Zhang, Jun.(2014).Smurf2 Negatively Modulates RIG-I-Dependent Antiviral Response by Targeting VISA/MAVS for Ubiquitination and Degradation.JOURNAL OF IMMUNOLOGY,192(10),4758-4764.
MLA Pan, Yu,et al."Smurf2 Negatively Modulates RIG-I-Dependent Antiviral Response by Targeting VISA/MAVS for Ubiquitination and Degradation".JOURNAL OF IMMUNOLOGY 192.10(2014):4758-4764.
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