Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha

Biochem Biophys Res Commun. 2001 Oct 5;287(4):808-13. doi: 10.1006/bbrc.2001.5659.


Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that regulate a number of adaptive responses to low oxygen tension. They are composed of alpha- and beta-subunits that belong to the basic helix-loop-helix-PAS superfamily. Here we examined the expression of HIF-alpha subunit proteins in the human kidney and found that, in addition to HIF-1alpha and -2alpha, HIF-3alpha was also expressed. The sequence analysis revealed that, like mouse HIF-3alpha, human HIF-3alpha has high similarity with HIF-1alpha and -2alpha in the bHLH and PAS domains, but lacks structures for transactivation found in the C-terminus of HIF-1alpha and -2alpha. Furthermore, we performed reporter gene analysis and showed that HIF-3alpha suppresses hypoxia-inducible HIF-mediated gene expression. HIF-3alpha might be a negative regulator of hypoxia-inducible gene expression in the human kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • COS Cells
  • Gene Expression Regulation*
  • Genes, Reporter
  • Helix-Loop-Helix Motifs
  • Humans
  • Kidney / chemistry
  • Kidney / metabolism*
  • Mice
  • Molecular Sequence Data
  • Oxygen / metabolism
  • Protein Structure, Tertiary
  • Protein Subunits
  • Repressor Proteins
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Transfection


  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • HIF3A protein, human
  • Hif3a protein, mouse
  • Protein Subunits
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • endothelial PAS domain-containing protein 1
  • Oxygen

Associated data

  • GENBANK/AB054067