Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Cell Hypoxia
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Cell Line
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Cobalt / pharmacology
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Deferoxamine / pharmacology
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Humans
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Hydroxylation
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Hydroxyproline / metabolism*
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Ligases*
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Mass Spectrometry
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Mice
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Molecular Sequence Data
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Oxygen / physiology*
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Protein Structure, Tertiary
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Proteins / metabolism*
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Recombinant Fusion Proteins / metabolism
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
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Ubiquitin-Protein Ligases*
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Ubiquitins / metabolism
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Von Hippel-Lindau Tumor Suppressor Protein
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Proteins
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Recombinant Fusion Proteins
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Trans-Activators
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Transcription Factors
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Tumor Suppressor Proteins
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Ubiquitins
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endothelial PAS domain-containing protein 1
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Cobalt
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Ubiquitin-Protein Ligases
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Von Hippel-Lindau Tumor Suppressor Protein
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Ligases
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VHL protein, human
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cobaltous chloride
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Deferoxamine
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Hydroxyproline
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Oxygen