pVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation
Du, Juan1; Zhang, Dawei1; Zhang, Wei1; Ouyang, Gang1; Wang, Jing1; Liu, Xing1; Li, Shun1; Ji, Wei1; Liu, Wei2; Xiao, Wuhan1,2
2015-08-15
Source PublicationJOURNAL OF IMMUNOLOGY
ISSN0022-1767
Volume195Issue:4Pages:1782-1790
AbstractThe 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.
SubtypeArticle
DOI10.4049/jimmunol.1500588
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaImmunology
WOS SubjectImmunology
WOS KeywordPRION-LIKE POLYMERIZATION ; TUMOR-SUPPRESSOR PROTEIN ; HIPPEL-LINDAU PROTEIN ; CELL RENAL-CARCINOMA ; I-LIKE RECEPTORS ; NF-KAPPA-B ; ADAPTER PROTEIN ; INNATE IMMUNITY ; VIRUS ; ACTIVATION
WOS IDWOS:000360013200048
Citation statistics
Cited Times:14[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/27147
Collection藻类生物学及应用研究中心_水生生物分子与细胞生物学研究中心
Affiliation1.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
Recommended Citation
GB/T 7714
Du, Juan,Zhang, Dawei,Zhang, Wei,et al. pVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation[J]. JOURNAL OF IMMUNOLOGY,2015,195(4):1782-1790.
APA Du, Juan.,Zhang, Dawei.,Zhang, Wei.,Ouyang, Gang.,Wang, Jing.,...&Xiao, Wuhan.(2015).pVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation.JOURNAL OF IMMUNOLOGY,195(4),1782-1790.
MLA Du, Juan,et al."pVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation".JOURNAL OF IMMUNOLOGY 195.4(2015):1782-1790.
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