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