[Cellular and tissue hypoxia--role of the von Hippel Lindau gene and hypoxia-inducible factor-1].
Hypoxia results in increased expression of some genes. This can compensate effects of hypoxia on the organism, and adapt cells and tissues to the environment with low oxygen tension. Mechanisms of cell and tissue responses to hypoxia have been extensively studied last years. The first identified mediator of cell response to hypoxia was hypoxia-inducible factor (HIF-1), which is being up regulated during hypoxic conditions. It binds to regulatory regions of sensitive genes and increases their transcription rate. Other key elements of cell response to hypoxia have been described recently--von Hippel-Lindau protein and prolyl hydroxylases, that allow degradation of alpha-subunit of HIF-1 during normal oxygen tension. This can ensure low level of HIF-1 in cells under physiological oxygen tension thus the expression of target genes is maintained on basal level. These new findings are starting points for further research and possible therapeutic use.
Sýkora
V
V
Ustav patologické fyziologie 1. LF UK, Praha. sikora@cesnet.cz
Necas
E
E
D015687:Cell Hypoxia / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010100:Oxygen / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*; 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; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D010100:Oxygen