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Experimental Physiology 91.5 pp 803-806
DOI: 10.1113/expphysiol.2006.033498
© The Physiological Society 2006
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Symposium Reports

Novel partners and mechanisms in oxygen sensing

Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia-inducible factor 1

Gregg L. Semenza1

1 Vascular Biology Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology and Radiation Oncology; and McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor composed of HIF-1{alpha} and HIF-1ß subunits that functions as a master regulator of oxygen homeostasis. Oxygen-dependent hydroxylation of HIF-1{alpha} provides a mechanism that allows changes in oxygenation to be transduced to the nucleus, leading to changes in gene expression. Hypoxia-inducible factor 1 plays critical roles in development, physiology and disease pathogenesis. Analyses of mice that are heterozygous for a null allele at the locus encoding the HIF-1{alpha} subunit have demonstrated that partial deficiency of HIF-1 is sufficient to impair multiple physiological responses to continuous and intermittent hypoxia.

(Received 17 April 2006; accepted after revision 10 May 2006; first published online 1 June 2006)
Corresponding author G. L. Semenza: Broadway Research Building, Suite 671, 733 N. Broadway, Baltimore, MD 21205, USA. Email: gsemenza{at}jhmi.edu




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