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Int. J. Mol. Sci. 2016, 17(12), 2003; doi:10.3390/ijms17122003

Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma

1
Cancer Research Center-IBMCC (USAL-CSIC), 37007 Salamanca, Spain
2
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
3
National Medicines Institute, 00725 Warsaw, Poland
4
Hematology Department, University Hospital of Salamanca, 37007 Salamanca, Spain
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Tomoo Iwakuma
Received: 29 September 2016 / Revised: 14 November 2016 / Accepted: 22 November 2016 / Published: 30 November 2016
(This article belongs to the Special Issue Emerging Non-Canonical Functions and Regulation of p53)
View Full-Text   |   Download PDF [714 KB, uploaded 30 November 2016]   |  

Abstract

The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation. Translational implications for MM and cancer prognosis and treatment are also reviewed. View Full-Text
Keywords: p53; myeloma; cancer; TP53 mutations; epigenetics; TP53 methylation; TP53 splicing; miRNAs; p53-based therapy p53; myeloma; cancer; TP53 mutations; epigenetics; TP53 methylation; TP53 splicing; miRNAs; p53-based therapy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Herrero, A.B.; Rojas, E.A.; Misiewicz-Krzeminska, I.; Krzeminski, P.; Gutiérrez, N.C. Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma. Int. J. Mol. Sci. 2016, 17, 2003.

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