Up-regulation of hypoxia-inducible factor-1alpha is not sufficient for hypoxic/anoxic p53 induction

Cancer Res. 1998 Dec 15;58(24):5678-80.


Oxygen-deprived regions of a solid tumor can induce tumor suppressor p53 expression and hence select for p53-mutant tumor cells with diminished apoptotic potential. It has been proposed that the hypoxia-inducible factor-1 (HIF-1) alpha subunit binds to p53 and protects it from proteasomal degradation. However, we found that hypoxic conditions that strongly induce HIF-1-dependent endogenous gene expression as well as HIF-1alpha protein neither induce p53-dependent gene expression nor p53 protein. The iron chelator deferoxamine induced both HIF-1alpha and p53, but p53 up-regulation could still be detected in HIF-1alpha-deficient cells, suggesting that mechanisms other than HIF-1alpha activation contribute to oxygen-regulated p53 induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Cell Hypoxia*
  • DNA-Binding Proteins / metabolism*
  • Deferoxamine / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Genes, p53*
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mice
  • Nuclear Proteins / metabolism*
  • Receptors, Aryl Hydrocarbon*
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • Up-Regulation


  • ARNT protein, human
  • Arnt protein, mouse
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Receptors, Aryl Hydrocarbon
  • Transcription Factors
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Deferoxamine