Biology of hypoxia-inducible factor-2alpha in development and disease

Cell Death Differ. 2008 Apr;15(4):628-34. doi: 10.1038/cdd.2008.17. Epub 2008 Feb 15.


The transcriptional response to hypoxia is primarily mediated by two hypoxia-inducible factors--HIF-1alpha and HIF-2alpha. While these proteins are highly homologous, increasing evidence suggests they have unique transcriptional targets and differential impact on tumor growth. Furthermore, non-transcriptional effects of the HIF-alpha subunits, including effects on the Notch and c-Myc pathways, contribute to their distinct functions. HIF-2alpha transcriptional targets include genes involved in erythropoiesis, angiogenesis, metastasis, and proliferation. Therefore, HIF-2alpha contributes significantly to both normal physiology as well as tumorigenesis. Here, we summarize the function of HIF-2alpha during development as well as its contribution to pathologic conditions, such as tumors and vascular disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Hypoxia
  • Cell Transformation, Neoplastic / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Mice
  • Mice, Knockout
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Phenotype
  • Signal Transduction*
  • Tissue Distribution
  • Transcription, Genetic


  • Basic Helix-Loop-Helix Transcription Factors
  • endothelial PAS domain-containing protein 1