Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression.
Although it was known for a long time that oxygen deprivation leads to the transcriptional induction of the gene encoding erythropoietin, the molecular mechanisms behind this process remained enigmatic. The cloning of the hypoxia-inducible factors (HIFs), the finding that HIF-1 regulates the expression of many more genes apart from erythropoietin, and the elucidation of the oxygen-dependent mechanisms degrading the HIF alpha subunits recently led to the spectacular discovery of the molecular principles of oxygen sensing. This review aims to summarize our current knowledge of oxygen-regulated gene expression..
Wenger
Roland H
RH
Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany. wenr@medizin.uni-leipzig.de
D000222:Adaptation, Physiological; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007501:Iron / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism* / Q000502:physiology*; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
C497396:ARNT protein, human; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D007501:Iron; D006899:Mixed Function Oxygenases; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human; D005947:Glucose; D010100:Oxygen