PT  - JOURNAL ARTICLE
AU  - Patrick H Maxwell
TI  - Oxygen homeostasis and cancer: insights from a rare disease
AID  - 10.7861/clinmedicine.2-4-356
DP  - 2002 Jul 01
TA  - Clinical Medicine
PG  - 356--362
VI  - 2
IP  - 4
4099  - http://www.rcpjournals.org/content/2/4/356.short
4100  - http://www.rcpjournals.org/content/2/4/356.full
SO  - Clin Med2002 Jul 01; 2
AB  - 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.