From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the hypoxia signal pathway.
The regulation of blood red cell production by the hormone erythropoietin (Epo) provides a paradigm for control of gene expression by oxygen. Analysis of this pathway has revealed a widespread system of gene regulation based on a transcriptional complex termed hypoxia-inducible factor (HIF). Hydroxylation of specific prolyl and asparinyl residues in the alpha subunit of HIF by a series of non-haem iron-dependent dioxygenases has been defined as a novel mechanism of protein modification that transduces the oxygen-sensitive signal.
Ratcliffe
Peter J
PJ
Renal and Cell Physiology Group, The Henry Wellcome Building of Genomic Medicine, University of Oxford, UK. pjr@well.ox.ac.uk
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004921:Erythropoietin / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008025:Ligases / Q000378:metabolism; D006899:Mixed Function Oxygenases; D009687:Nuclear Proteins / Q000378:metabolism; D010100:Oxygen / Q000502:physiology*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004921:Erythropoietin; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D011393:Procollagen-Proline Dioxygenase; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human; D010100:Oxygen