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

Authors

  • Anna-Liisa Nieminen,

    Corresponding author
    1. Department of Anatomy and Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio
    • Case Comprehensive Cancer Center Laboratories, 3-134 Wolstein Research Building, 10900 Euclid Avenue, Cleveland, Ohio 44106-7285.
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  • Suparna Qanungo,

    1. Department of Anatomy and Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio
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  • Elizabeth A. Schneider,

    1. Department of Anatomy and Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio
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  • Bing-Hua Jiang,

    1. Department of Microbiology, Immunology and Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia
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  • Faton H. Agani

    Corresponding author
    1. Department of Anatomy and Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio
    • 322 Biomedical Research Building, 10900 Euclid Avenue, Cleveland, Ohio 44106.
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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.

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