Mdm2 and HIF‐1α interaction in tumor cells during hypoxia

Abstract The interaction between HIF‐1α, Mdm2, and p53 proteins during hypoxia has received recent attention. Here, we investigated the consequences of interaction between HIF‐1α and Mdm2 under hypoxic conditions. Endogenous HIF‐1α 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‐1α 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. © 2005 Wiley‐Liss, Inc.