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题名: pVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation
作者: Du, Juan1; Zhang, Dawei1; Zhang, Wei1; Ouyang, Gang1; Wang, Jing1; Liu, Xing1; Li, Shun1; Ji, Wei1; Liu, Wei2; Xiao, Wuhan1, 2
刊名: JOURNAL OF IMMUNOLOGY
发表日期: 2015-08-15
DOI: 10.4049/jimmunol.1500588
卷: 195, 期:4, 页:1782-1790
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
类目[WOS]: Immunology
研究领域[WOS]: Immunology
英文摘要: The von Hippel-Lindau (VHL) gene is a well-defined tumor suppressor linked to human heredity cancer syndromes. As a component of the VHL-elongin B/C E3 ligase complex, pVHL performs its tumor function by targeting proteins for proteasomal degradation. It is largely unknown whether pVHL functions in antiviral immunity. In this article, we identify that pVHL negatively regulates innate antiviral immunity, which acts mainly by inducing degradation of mitochondrial antiviral-signaling protein (MAVS, also known as Cardif, IPS-1, or VISA). Overexpression of pVHL abrogated the cellular response to viral infection, whereas knockdown of pVHL exerted the opposite effect. pVHL targeted the K420 residue of MAVS to catalyze the formation of K48-linked polyubiquitin chains, leading to proteasomal degradation of MAVS. After viral infection, Mavs levels remained low in wild type zebrafish embryos but became much higher in vhl-deficient (vhl(-/-)) zebrafish embryos. Higher MAVS levels correlated with a greatly exaggerated antiviral response. In this work, we demonstrate that pVHL exhibits a previously unknown role in innate antiviral immunity.
关键词[WOS]: PRION-LIKE POLYMERIZATION ; TUMOR-SUPPRESSOR PROTEIN ; HIPPEL-LINDAU PROTEIN ; CELL RENAL-CARCINOMA ; I-LIKE RECEPTORS ; NF-KAPPA-B ; ADAPTER PROTEIN ; INNATE IMMUNITY ; VIRUS ; ACTIVATION
语种: 英语
WOS记录号: WOS:000360013200048
ISSN号: 0022-1767
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/27147
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Hubei Province, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei Province, Peoples R China
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