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Crosstalk Between Mdm2, p53 and HIF1-α: Distinct Responses to Oxygen Stress and Implications for Tumour Hypoxia

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Mutant p53 and MDM2 in Cancer

Part of the book series: Subcellular Biochemistry ((SCBI,volume 85))

Abstract

The E3 ubiquitin ligase Mdm2 regulates two transcription factors, p53 and HIF1α, which appear to be tailored towards different and specific roles within the cell, the DNA damage and hypoxia responses, respectively. However, evidence increasingly points towards the interplay between these factors being crucial for the regulation of cellular metabolism and survival in times of oxygen stress, which has particular relevance for tumour formation. Mdm2, p53 and HIF1α all respond to hypoxia, and intriguingly, have distinct roles depending on the level of hypoxia. The data from numerous studies across different conditions hint at the interplay between these key factors in cellular homeostasis. Here we try to weave these strands together, to create a picture of the complex tapestry of interactions that demonstrates the importance of the crosstalk between these key regulatory proteins during hypoxia.

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Acknowledgments

E. Douglas Robertson is a recipient of an INCa (HypoNet project) post-doctoral fellowship, and Kostyantyn Semenchenko PhD fellowships from the FP7 Marie Curie ITN Cancure and the Association pour la Recherche sur le Cancer. Research in the laboratory of B. Wasylyk is supported by the CNRS, INSERM, the Association pour la Recherche sur le Cancer, the University of Strasbourg, the Institut National du Cancer (INCa), the Ligue Nationale contre le Cancer and the Conférence de Coordination Interrégionale du Grand Est de la Ligue contre le Cancer.

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  1. Department of Functional Genomics and Cancer Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire IGBMC, UMR 7104 CNRS-UdS, U946 INSERM, 1 rue Laurent Fries, BP 10142, 67404, Illkirch Cedex, France

    E. Douglas Robertson, Kostyantyn Semenchenko & Bohdan Wasylyk

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Correspondence to Bohdan Wasylyk .

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  1. Department of Biochemistry and Molecular Biology, and the Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA

    Swati Palit Deb

  2. Department of Biochemistry and Molecular Biology, and the Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA

    Sumitra Deb

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Robertson, E.D., Semenchenko, K., Wasylyk, B. (2014). Crosstalk Between Mdm2, p53 and HIF1-α: Distinct Responses to Oxygen Stress and Implications for Tumour Hypoxia. In: Deb, S., Deb, S. (eds) Mutant p53 and MDM2 in Cancer. Subcellular Biochemistry, vol 85. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9211-0_11

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