Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel - Lindau protein Journal Article
| Authors: | Ohh, M.; Park, C. W.; Ivan, M.; Hoffman, M. A.; Kim, T. Y.; Huang, L. E.; Pavletich, N.; Chau, V.; Kaelin, W. G. |
| Article Title: | Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel - Lindau protein |
| Abstract: | von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome that is characterized by the development of multiple vascular tumors and is caused by inactivation of the von Hippel-Lindau protein (pVHL). Here we show that pVHL, through its β-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in an α-domain-dependent manner. This is the first function to be ascribed to the pVHL β-domain. Furthermore, we provide the first direct evidence that pVHL has a function analogous to that of an F-box protein, namely, to recruit substrates to a ubiquitination machine. These results strengthen the link between overaccumulation of HIF and development of VHL disease. |
| Keywords: | unclassified drug; human cell; mutation; dna-binding proteins; ubiquitin; protein domain; proteins; oxygen; cell protein; protein binding; tumor cells, cultured; hela cells; transfection; carcinogenesis; transcription factors; nuclear proteins; protein processing; protein processing, post-translational; tumor suppressor proteins; vascular tumor; familial cancer; protein structure, tertiary; von hippel lindau disease; ubiquitin-protein ligases; deferoxamine; von hippel lindau protein; cell extracts; hypoxia-inducible factor 1, alpha subunit; ubiquitins; ligases; hypoxia inducible factor 1; hypoxia-inducible factor 1; f box protein; von hippel-lindau tumor suppressor protein; humans; human; priority journal; article |
| Journal Title: | Nature Cell Biology |
| Volume: | 2 |
| Issue: | 7 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2000-07-01 |
| Start Page: | 423 |
| End Page: | 427 |
| Language: | English |
| DOI: | 10.1038/35017054 |
| PUBMED: | 10878807 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
