| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Liu, Xing Zhang, Dawei Liu, Wei Zhang, Wei Ouyang, Gang Li, Shun Du, Juan Wang, Jing Ji, Wei Xiao, Wuhan |
| Description |
Author Affiliation: Du J ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China); Zhang D ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China); Zhang W ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China); Ouyang G ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China); Wang J ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China); Liu X ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China); Li S ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China); Ji W ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China); Liu W ( State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China.); Xiao W ( Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China) |
| 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. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-08-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Adaptor Proteins, Signal Transducing Metabolism Proteasome Endopeptidase Complex Signal Transduction Von Hippel-lindau Tumor Suppressor Protein Chemistry Animals Animals, Genetically Modified Cell Line Gene Knockout Techniques Immunity, Innate Protein Binding Proteolysis Genetics Zebrafish Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
