Mdm2 and HIF-1alpha interaction in tumor cells during hypoxia

J Cell Physiol. 2005 Aug;204(2):364-9. doi: 10.1002/jcp.20406.


The interaction between HIF-1alpha, Mdm2, and p53 proteins during hypoxia has received recent attention. Here, we investigated the consequences of interaction between HIF-1alpha and Mdm2 under hypoxic conditions. Endogenous HIF-1alpha and Mdm2 proteins were co-immunoprecipitated from lysates of hypoxic HCT116 p53WT and p53(-/-) cells, suggesting that association of these two proteins is a p53-independent event. The cellular Mdm2 protein content was not significantly altered in hypoxic tumor cells. Overexpression of Mdm2 resulted in an increase in HIF-1alpha protein content in hypoxic cells and increased hypoxia-induced vascular endothelial growth factor (VEGF) transcriptional activation. These results point toward a novel and p53-independent function of Mdm2 to promote tumor cell adaptations to hypoxia by interacting with and promoting HIF-1 activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Hypoxia / genetics
  • Cells, Cultured
  • Drug Interactions
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mice
  • Neoplasms / metabolism*
  • Nuclear Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism


  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2