HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.

Dana-Farber Cancer Institute and Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing.
Mesh Terms:
Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Hypoxia, Cell Line, Cobalt, Deferoxamine, Humans, Hydroxylation, Hydroxyproline, Ligases, Mass Spectrometry, Mice, Molecular Sequence Data, Oxygen, Protein Structure, Tertiary, Proteins, Recombinant Fusion Proteins, Trans-Activators, Transcription Factors, Tumor Cells, Cultured, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Ubiquitins, Von Hippel-Lindau Tumor Suppressor Protein
Science Apr. 20, 2001; 292(5516);464-8 [PUBMED:11292862]
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