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Cooperation of p53 Mutations with Other Oncogenic Alterations in Cancer

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Mutant p53 and MDM2 in Cancer

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

Abstract

Following the initial findings suggesting a pro-oncogenic role for p53 point mutants, more than 30 years of research have unveiled the critical role exerted by these mutants in human cancer. A growing body of evidence, including mouse models and clinical data, has clearly demonstrated a connection between mutant p53 and the development of aggressive and metastatic tumors. Even if the molecular mechanisms underlying mutant p53 activities are still the object of intense scrutiny, it seems evident that full activation of its oncogenic role requires the functional interaction with other oncogenic alterations. p53 point mutants, with their pleiotropic effects, simultaneously activating several mechanisms of aggressiveness, are engaged in multiple cross-talk with a variety of other cancer-related processes, thus depicting a complex molecular landscape for the mutant p53 network. In this chapter revealing evidence illustrating different ways through which this cooperation may be achieved will be discussed. Considering the proposed role for mutant p53 as a driver of cancer aggressiveness, disarming mutant p53 function by uncoupling the cooperation with other oncogenic alterations, stands out as an exciting possibility for the development of novel anti-cancer therapies.

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Authors and Affiliations

  1. Molecular Oncology Group, Institute of Molecular and Cell Biology of Rosario, IBR-CONICET, Rosario, Argentina

    Javier E. Girardini

  2. Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste, Italy

    Dawid Walerych & Giannino Del Sal

  3. Dipartimento di Scienze della Vita, Università degli Studi di Trieste, 34127, Trieste, Italy

    Dawid Walerych & Giannino Del Sal

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  2. Dawid Walerych
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  3. Giannino Del Sal
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Correspondence to Giannino Del Sal .

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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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© 2014 Springer Science+Business Media Dordrecht

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Girardini, J.E., Walerych, D., Del Sal, G. (2014). Cooperation of p53 Mutations with Other Oncogenic Alterations in Cancer. 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_3

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