HIF-1 and HIF-2 transcription factors--similar but not identical

Mol Cells. 2010 May;29(5):435-42. doi: 10.1007/s10059-010-0067-2. Epub 2010 Apr 12.


Hypoxia inducible factor (HIF)-1 and HIF-2 are heterodimeric transcription factors mediating the cellular response to hypoxia. Recent data indicate that not only ubiquitous HIF-1 alpha, but also more cell-specific HIF-2 alpha, is an important regulator of the hypoxia response. Although both alpha subunits are highly conservative at protein level, share similar domain structure, heterodimerize with HIF-1 beta, and bind to the same DNA sequence called hypoxia responsive element (HRE), their effect on the expression of some genes may vary. In this review we stressed the differences between the isoforms, their structure and expression pattern. Moreover, we described diversity of coactivators and proteins which interact with HIFs, and which are responsible for the specificity of their action. Finally, recent data showing link between HIFs and specific microRNA have been presented.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Hypoxia / physiology
  • Gene Expression Regulation
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • MicroRNAs / genetics
  • Protein Conformation
  • Protein Stability
  • Protein Structure, Tertiary / genetics
  • Ubiquitination
  • p300-CBP Transcription Factors / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MicroRNAs
  • endothelial PAS domain-containing protein 1
  • p300-CBP Transcription Factors