TY - JOUR T1 - Oxygen homeostasis and cancer: insights from a rare disease JF - Clinical Medicine JO - Clin Med SP - 356 LP - 362 DO - 10.7861/clinmedicine.2-4-356 VL - 2 IS - 4 AU - Patrick H Maxwell Y1 - 2002/07/01 UR - http://www.rcpjournals.org/content/2/4/356.abstract N2 - 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 signallingred cell production via erythropoietincellular 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 HIF 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. ER -