HIF-1's relationship to oxygen: simple yet sophisticated.
HIF-1 is a transcription factor which acts as a master regulator coordinating oxygen homeostasis. An oxygen sensitive signal controlling HIF-1 is provided by enzymatic hydroxylation reactions which require molecular oxygen and modify specific prolyl and asparaginyl residues in the HIF a subunit. These act as switches-- enabling capture by a specific ubiquitin ligase and preventing transactivator recruitment. An important challenge is to understand how this simple principle is used to tailor the oxygen response system to the diverse settings that occur in complex organisms such as ourselves. The emerging picture is of many parameters which are likely to contribute, including cofactor availability and regulated expression of the hydroxylase enzymes.
Maxwell
Patrick H
PH
Imperial College, Renal Section, Hammersmith Campus, London, United Kingdom. p.maxwell@imperial.ac.uk
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000075065:Elongin; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007680:Kidney Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D004268:DNA-Binding Proteins; D000075065:Elongin; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D021122:Protein Subunits; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D011393:Procollagen-Proline Dioxygenase; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D010100:Oxygen