• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.

Hypoxia-inducible factor (HIF) is a transcriptional complex that plays a central role in the regulation of gene expression by oxygen. In oxygenated and iron replete cells, HIF-alpha subunits are rapidly destroyed by a mechanism that involves ubiquitylation by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex. This process is suppressed by hypoxia and iron chelation, allowing transcriptional activation. Here we show that the interaction between human pVHL and a specific domain of the HIF-1alpha subunit is regulated through hydroxylation of a proline residue (HIF-1alpha P564) by an enzyme we have termed HIF-alpha prolyl-hydroxylase (HIF-PH). An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor.

Pubmed ID: 11292861


  • Jaakkola P
  • Mole DR
  • Tian YM
  • Wilson MI
  • Gielbert J
  • Gaskell SJ
  • von Kriegsheim A
  • Hebestreit HF
  • Mukherji M
  • Schofield CJ
  • Maxwell PH
  • Pugh CW
  • Ratcliffe PJ


Science (New York, N.Y.)

Publication Data

April 20, 2001

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Ascorbic Acid
  • Cell Hypoxia
  • DNA-Binding Proteins
  • Deferoxamine
  • Ferrous Compounds
  • Humans
  • Hydroxylation
  • Hydroxyproline
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ligases
  • Molecular Sequence Data
  • Nuclear Proteins
  • Oxygen
  • Point Mutation
  • Procollagen-Proline Dioxygenase
  • Protein Structure, Tertiary
  • Proteins
  • Recombinant Fusion Proteins
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transcription Factors
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases
  • Ubiquitins
  • Von Hippel-Lindau Tumor Suppressor Protein