Oxygen sensors and angiogenesis.
SEMIN CELL DEV BIOL
29 - 37.
Local oxygen tension has a profound effect on the vasculature, which compensates vascular insufficiency through the induction of angiogenesis. An important mediator in this Process is the hypoxia-inducible factor (HIF) complex, which is activated in hypoxic cells and increases transcription of a broad range of genes including angiogenic growth factors such as VEGF HIF is primarily regulated through oxygen-dependent proteasomal destruction of the regulatory subunit, HIF-1alpha or HIF-2alpha. Regulation is through the modification of specific prolines in HIF-alpha chains which are hydroxylated by a recently identified family of enzymes which require molecular oxygen and 2-oxoglutarate as cosubstrates, and iron as a cofactor. Following modification HIF-alpha chains are captured by a ubiquitin ligase E3 complex containing the von Hippel-Lindau (VHL) tumour suppressor protein. The HIF prolyl hydroxylases (PHD enzymes) act as oxygen sensors regulating HIF, and hence angiogenesis. The PFM-HIF-VHL system provides a range of opportunities for therapeutic manipulation.
|Title:||Oxygen sensors and angiogenesis|
|Keywords:||HIF, prolyl hydroxylase, oxygen sensor, angiogenesis, von Hippel-Lindau, LINDAU TUMOR-SUPPRESSOR, INDUCIBLE FACTOR 1-ALPHA, ENDOTHELIAL GROWTH-FACTOR, TRANSCRIPTION FACTOR, CAENORHABDITIS-ELEGANS, PROLYL HYDROXYLATION, ERYTHROPOIETIN GENE, SIGNAL-TRANSDUCTION, TRANSGENIC MICE, ALPHA-SUBUNIT|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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