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Mechanisms of Mutant p53 Stabilization in Cancer

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Mutant p53 and MDM2 in Cancer

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

Abstract

p53 transactivates cell cycle inhibitory, apoptosis or senescence-related genes in response to DNA damage to protect the genetic integrity of the cell. Highlighting its critical tumor suppressor functions, p53 is mutated, lost, or functionally inactivated in nearly all cancers. When mutated within its core DNA binding domain, p53’s normal instability is abrogated, and oncogenic gain-of-function properties are observed accompanied by massive accumulation of steady state mutant p53 protein levels relative to the low or undetectable steady state level of wild-type (WT) p53 in normal cells. Mutation of p53 may affect its stability through a combination of mutant p53’s inherent biochemical and biophysical properties as well as pathways aberrantly activated in genetically damaged cells. The increased stability of mutant p53 proteins is key to its ability to accumulate to high levels and phenotypically exhibit “gain-of-function” properties. In this chapter we will address the multifaceted ways in which intrinsic mutant p53 properties intersect with emergent properties of cancer cells to yield the stable mutant p53 phenotype.

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Author information

Authors and Affiliations

  1. Division of Hematology, Oncology, and Palliative Care, VCU Massey Cancer Center, Virginia Commonwealth University, 1201 E. Marshall St., Box 980070, Richmond, VA, 23298, USA

    Rebecca A. Frum & Steven R. Grossman

Authors
  1. Rebecca A. Frum
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  2. Steven R. Grossman
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Corresponding author

Correspondence to Steven R. Grossman .

Editor information

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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Frum, R.A., Grossman, S.R. (2014). Mechanisms of Mutant p53 Stabilization 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_10

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