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 Publication | JOURNAL OF IMMUNOLOGY
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ISSN | 0022-1767 |
Volume | 195Issue:4Pages:1782-1790 |
Abstract | 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. |
Subtype | Article |
DOI | 10.4049/jimmunol.1500588 |
WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
Indexed By | SCI |
Language | 英语 |
WOS Research Area | Immunology |
WOS Subject | Immunology |
WOS ID | WOS:000360013200048 |
WOS Keyword | PRION-LIKE POLYMERIZATION ; TUMOR-SUPPRESSOR PROTEIN ; HIPPEL-LINDAU PROTEIN ; CELL RENAL-CARCINOMA ; I-LIKE RECEPTORS ; NF-KAPPA-B ; ADAPTER PROTEIN ; INNATE IMMUNITY ; VIRUS ; ACTIVATION |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ihb.ac.cn/handle/342005/27147 |
Collection | 水生生物分子与细胞生物学研究中心_期刊论文 |
Affiliation | 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 |
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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