Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein.
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 beta-domain, binds directly to hypoxia-inducible factor (HIF), thereby targeting HIF for ubiquitination in ... an alpha-domain-dependent manner. This is the first function to be ascribed to the pVHL beta-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.
Mesh Terms:
Cell Extracts, DNA-Binding Proteins, Deferoxamine, Hela Cells, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Ligases, Mutation, Nuclear Proteins, Oxygen, Protein Binding, Protein Processing, Post-Translational, Protein Structure, Tertiary, Proteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Ubiquitins, Von Hippel-Lindau Tumor Suppressor Protein
Cell Extracts, DNA-Binding Proteins, Deferoxamine, Hela Cells, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Ligases, Mutation, Nuclear Proteins, Oxygen, Protein Binding, Protein Processing, Post-Translational, Protein Structure, Tertiary, Proteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Ubiquitins, Von Hippel-Lindau Tumor Suppressor Protein
Nat. Cell Biol.
Date: Jul. 01, 2000
PubMed ID: 10878807
View in: Pubmed Google Scholar
Download Curated Data For This Publication
116590
Switch View:
- Interactions 3