Abstract
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic-helix-loop-helix-PAS transcription factor consisting of HIF-1α and HIF-1β subunits. HIF-1α expression and HIF-1 transcriptional activity increase exponentially as cellular O2 concentration is decreased. Several dozen target genes that are transactivated by HIF-1 have been identified, including those encoding erythropoietin, glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. The products of these genes either increase O2 delivery or allow metabolic adaptation to reduced O2 availability. HIF-1 is required for cardiac and vascular development and embryonic survival. In fetal and postnatal life, HIF-1 is required for a variety of physiological responses to chronic hypoxia. HIF-1 expression is increased in tumor cells by multiple mechanisms and may mediate adaptation to hypoxia that is critical for tumor progression. HIF-1 thus appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology.
Original language | English (US) |
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Pages (from-to) | 551-578 |
Number of pages | 28 |
Journal | Annual Review of Cell and Developmental Biology |
Volume | 15 |
DOIs | |
State | Published - 1999 |
Keywords
- Cardiovascular development
- Ischemia
- Oxygen
- Transcription
- Tumor progression
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology