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Int. J. Mol. Sci. 2017, 18(5), 928; doi:10.3390/ijms18050928

Significance of Wild-Type p53 Signaling in Suppressing Apoptosis in Response to Chemical Genotoxic Agents: Impact on Chemotherapy Outcome

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
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Academic Editors: Ashis Basu and Takehiko Nohmi
Received: 20 March 2017 / Revised: 18 April 2017 / Accepted: 25 April 2017 / Published: 28 April 2017
(This article belongs to the Special Issue Chemically-Induced DNA Damage, Mutagenesis, and Cancer)
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Abstract

Our genomes are subject to potentially deleterious alterations resulting from endogenous sources (e.g., cellular metabolism, routine errors in DNA replication and recombination), exogenous sources (e.g., radiation, chemical agents), and medical diagnostic and treatment applications. Genome integrity and cellular homeostasis are maintained through an intricate network of pathways that serve to recognize the DNA damage, activate cell cycle checkpoints and facilitate DNA repair, or eliminate highly injured cells from the proliferating population. The wild-type p53 tumor suppressor and its downstream effector p21WAF1 (p21) are key regulators of these responses. Although extensively studied for its ability to control cell cycle progression, p21 has emerged as a multifunctional protein capable of downregulating p53, suppressing apoptosis, and orchestrating prolonged growth arrest through stress-induced premature senescence. Studies with solid tumors and solid tumor-derived cell lines have revealed that such growth-arrested cancer cells remain viable, secrete growth-promoting factors, and can give rise to progeny with stem-cell-like properties. This article provides an overview of the mechanisms by which p53 signaling suppresses apoptosis following genotoxic stress, facilitating repair of genomic injury under physiological conditions but having the potential to promote tumor regrowth in response to cancer chemotherapy. View Full-Text
Keywords: chemical genotoxic agents; p53 signaling; p21WAF1 (CDKN1A); DNAJB9; multinucleated giant cells; premature senescence; apoptosis; mutational processes chemical genotoxic agents; p53 signaling; p21WAF1 (CDKN1A); DNAJB9; multinucleated giant cells; premature senescence; apoptosis; mutational processes
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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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Mirzayans, R.; Andrais, B.; Kumar, P.; Murray, D. Significance of Wild-Type p53 Signaling in Suppressing Apoptosis in Response to Chemical Genotoxic Agents: Impact on Chemotherapy Outcome. Int. J. Mol. Sci. 2017, 18, 928.

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