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学科主题: 基础医学
题名:
Smurf2 Negatively Modulates RIG-I-Dependent Antiviral Response by Targeting VISA/MAVS for Ubiquitination and Degradation
作者: Pan, Yu; Li, Rui; Meng, Jun-Ling; Mao, He-Ting; Zhang, Yu; Zhang, Jun
刊名: JOURNAL OF IMMUNOLOGY
发表日期: 2014-05-15
DOI: 10.4049/jimmunol.1302632
卷: 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
所属项目编号: 2011CB946103 ; 2010CB945300
项目资助者: National Basic Research Program of China ; Program for New Century Excellent Talents in University
WOS记录号: WOS:000335973600033
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65222
Appears in Collections:基础医学院_免疫学系_期刊论文

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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

Recommended Citation:
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.
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