Oxygen homeostasis and cancer: insights from a rare disease.
356 - 362.
Many aspects of physiology and anatomy are precisely adjusted so that the right amount of oxygen reaches cells throughout the body. Hypoxia-inducible factor-1 (HIF-1) is activated by low oxygen tension in all mammalian cells and underpins many aspects of the impressive ability to match oxygen supply and demand. As examples, HIF-1 regulates:. local capillary architecture via angiogenic signalling. red cell production via erythropoietin. cellular metabolism via increased expression of glucose transporters and glycolytic enzymes.HIF-1 is also important in disease, for example in cancer where it is involved in angiogenesis. This review describes how HIF-1 is regulated by oxygen and the central role played by the von Hippel-Lindau tumour suppressor protein. The underlying oxygen sensor is provided by a family of enzymes which oxidise specific proline residues in HIFalpha subunits. Inhibiting these newly discovered enzymes provides a way of activating HIF-1 in the presence of oxygen - an exciting prospect for therapeutic intervention in ischaemic diseases.
|Title:||Oxygen homeostasis and cancer: insights from a rare disease|
|Keywords:||hypoxia-inducible factor-1, oxygen, ubiquitin, von Hippel-Lindau, TUMOR-SUPPRESSOR PROTEIN, ERYTHROPOIETIN-PRODUCING CELLS, HIPPEL-LINDAU PROTEIN, PROLYL HYDROXYLATION, GENE-EXPRESSION, REGULATE HIF, HYPOXIA, IDENTIFICATION, BINDING, COMPLEX|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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