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

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.

Pubmed ID: 11292862


  • Ivan M
  • Kondo K
  • Yang H
  • Kim W
  • Valiando J
  • Ohh M
  • Salic A
  • Asara JM
  • Lane WS
  • Kaelin WG


Science (New York, N.Y.)

Publication Data

April 20, 2001

Associated Grants


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