Expression of hypoxia-inducible factor 1: mechanisms and consequences

Publication Type:

Journal Article

Source:

Biochemical Pharmacology, Volume 59, Issue 1, p.47 - 53 (2000)

URL:

http://linkinghub.elsevier.com/retrieve/pii/S0006295299002920

Abstract:

Hypoxia-inducible factor 1 (HIF-1) is a basic-helix-loop-helix transcription factor that plays essential roles in mammalian development and physiology. HIF-1 is a heterodimer composed of HIF-1α and HIF-1β subunits. The expression and activity of the HIF-1α subunit are tightly regulated by cellular O2 concentration. Under hypoxic conditions, HIF-1 activates the transcription of genes encoding erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other genes whose protein products increase O2 delivery or facilitate metabolic adaptation to hypoxia. HIF-1 is essential for embryonic vascularization and survival, neovascularization in ischemic myocardium, hypoxia-induced pulmonary vascular remodeling, and tumor vascularization. HIF-1α is overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. Pharmacologic manipulation of HIF-1 levels may provide a novel therapeutic approach to diseases that represent the most common causes of mortality in Western society, including cancer, chronic lung disease, and myocardial ischemia.

National Library of Medicine (brackets, no "et al."): Semenza GL. Expression of hypoxia-inducible factor 1: mechanisms and consequences. Biochemical Pharmacology [Internet]. 2000;59(1):47 - 53. http://linkinghub.elsevier.com/retrieve/pii/S0006295299002920
National Library of Medicine (grant proposals with PMCID/PMID): Semenza GL. Expression of hypoxia-inducible factor 1: mechanisms and consequences. Biochemical Pharmacology [Internet]. 2000;59(1):47 - 53. http://linkinghub.elsevier.com/retrieve/pii/S0006295299002920
National Library of Medicine (NLM) - Grant with PMID: Semenza GL. Expression of hypoxia-inducible factor 1: mechanisms and consequences. Biochemical Pharmacology [Internet]. 2000;59(1):47 - 53. http://linkinghub.elsevier.com/retrieve/pii/S0006295299002920
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