The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis.

Journal article

Hypoxia-inducible factor-1 (HIF-1) has a key role in cellular responses to hypoxia, including the regulation of genes involved in energy metabolism, angiogenesis and apoptosis. The alpha subunits of HIF are rapidly degraded by the proteasome under normal conditions, but are stabilized by hypoxia. Cobaltous ions or iron chelators mimic hypoxia, indicating that the stimuli may interact through effects on a ferroprotein oxygen sensor. Here we demonstrate a critical role for the von Hippel-Lindau...

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Authors: Maxwell, P; Wiesener, MS; Chang, G; Clifford, S; Vaux, E

• Publication status: Published
• Journal: Nature
• Volume: 399
• Issue: 6733
• Pages: 271-275
• Publication date: 1999-05-01
• DOI: 10.1038/20459
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: Protein Binding; von Hippel-Lindau Disease; Hypoxia-Inducible Factor 1, alpha Subunit; Nuclear Proteins; Cobalt; Cell Hypoxia; Genes, Tumor Suppressor; Hela Cells; Neovascularization, Pathologic; Proteasome Endopeptidase Complex; Ligases; Tumor Cells, Cultured; Humans; Von Hippel-Lindau Tumor Suppressor Protein; Oxygen; Cysteine Endopeptidases; Hypoxia-Inducible Factor 1; Transfection; Response Elements; Ubiquitin-Protein Ligases; Iron Chelating Agents; Proteins; Tumor Suppressor Proteins; Multienzyme Complexes; Transcription Factors; Gene Expression Regulation; DNA-Binding Proteins