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p53-Independent Effects of Mdm2

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Mutant p53 and MDM2 in Cancer

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

Abstract

Mdm2 is best known as the primary negative regulator of p53, but a growing body of evidence suggests that Mdm2 also has a number of functions independent of its role in regulating p53. Although these functions are not yet well-characterized, they have been implicated in regulating of a number of cellular processes, including cell-cycle control, apoptosis, differentiation, genome stability, and transcription, among others. It appears that Mdm2 exerts these functions through a surprisingly wide variety of mechanisms. For example, it has been shown that Mdm2 can ubiquitinate alternative targets, can stimulate the activity of transcription factors, and can directly bind to mRNA to regulate its stability. Dysregulation of p53-independent functions could be responsible for the oncogenic properties of Mdm2 seen even in the absence of p53, and may explain why approximately 10 % of human tumors overexpress Mdm2 instead of inactivating p53 through other mechanisms. As the p53-independent functions of Mdm2 present novel targets for potential therapeutic interventions, fully characterizing these cellular and pathogenic roles of Mdm2 will be important in the study of tumor biology and the treatment of cancer.

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Authors and Affiliations

  1. Department of Oncological Sciences, The Graduate School of Biomedical Sciences Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Stephen Bohlman & James J. Manfredi

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  1. Stephen Bohlman
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  2. James J. Manfredi
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Correspondence to James J. Manfredi .

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Editors and Affiliations

  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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Bohlman, S., Manfredi, J.J. (2014). p53-Independent Effects of Mdm2. 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_13

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