Mdm2 and HIF-1alpha interaction in tumor cells during hypoxia.
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.
Mesh Terms:
Animals, Cell Hypoxia, Cells, Cultured, Drug Interactions, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Neoplasms, Nuclear Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Transcription Factors, Transcriptional Activation, Tumor Suppressor Protein p53
Animals, Cell Hypoxia, Cells, Cultured, Drug Interactions, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Neoplasms, Nuclear Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Transcription Factors, Transcriptional Activation, Tumor Suppressor Protein p53
J. Cell. Physiol.
Date: Aug. 01, 2005
PubMed ID: 15880652
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