Expression of hypoxia-inducible factor 1: Mechanisms and consequences

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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 O 2 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 O 2 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.

Original languageEnglish (US)
Pages (from-to)47-53
Number of pages7
JournalBiochemical Pharmacology
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2000

Keywords

  • Angiogenesis
  • Cancer
  • Ischemia
  • Oxygen homeostasis
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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