Two faces of p53: aging and tumor suppression

Rodier, F.; Campisi, J.; Bhaumik, D.

doi:10.1093/nar/gkm744

Title: Two faces of p53: aging and tumor suppression

Journal Article · Tue Oct 16 00:00:00 EDT 2007 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkm744· OSTI ID:1625429

Rodier, F. ^[1]; Campisi, J. ^[1]; Bhaumik, D. ^[2]

Buck Inst. for Age Research, Novato, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Buck Inst. for Age Research, Novato, CA (United States)

The p53 tumor suppressor protein, often termed guardian of the genome, integrates diverse physiological signals in mammalian cells. In response to stress signals, perhaps the best studied of which is the response to DNA damage, p53 becomes functionally active and triggers either a transient cell cycle arrest, cell death (apoptosis) or permanent cell cycle arrest (cellular senescence). Both apoptosis and cellular senescence are potent tumor suppressor mechanisms that irreversibly prevent damaged cells from undergoing neoplastic transformation. However, both processes can also deplete renewable tissues of proliferation-competent progenitor or stem cells. Such depletion, in turn, can compromise the structure and function of tissues, which is a hallmark of aging. Moreover, whereas apoptotic cells are by definition eliminated from tissues, senescent cells can persist, acquire altered functions, and thus alter tissue microenvironments in ways that can promote both cancer and aging phenotypes. Recent evidence suggests that increased p53 activity can, at least under some circumstances, promote organismal aging. Here, we discuss the role of p53 as a key regulator of the DNA damage responses, and discuss how p53 integrates the outcome of the DNA damage response to optimally balance tumor suppression and longevity.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-05CH11231; LB05-000446

OSTI ID:: 1625429

Journal Information:: Nucleic Acids Research, Vol. 35, Issue 22; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Molecular Dynamic Simulation Insights into the Normal State and Restoration of p53 Function Fu, Ting; Min, Hanyi; Xu, Yong International Journal of Molecular Sciences, Vol. 13, Issue 8 https://doi.org/10.3390/ijms13089709	journal	August 2012
Hypoxia, melanocytes and melanoma - survival and tumor development in the permissive microenvironment of the skin Bedogni, Barbara; Powell, Marianne Broome Pigment Cell & Melanoma Research, Vol. 22, Issue 2 https://doi.org/10.1111/j.1755-148X.2009.00553.x	journal	April 2009
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The Potential for Renal Injury Elicited by Physical Work in the Heat Schlader, Zachary J.; Hostler, David; Parker, Mark D. Nutrients, Vol. 11, Issue 9 https://doi.org/10.3390/nu11092087	journal	September 2019
TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants Sulak, Michael; Fong, Lindsey; Mika, Katelyn eLife, Vol. 5 https://doi.org/10.7554/elife.11994	journal	September 2016
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Clinically Relevant Doses of Chemotherapy Drugs Selectively and Reversibly Block Glioblastoma Neurosphere Proliferation in vitro: A Dissertation Mihaliak, Alicia M. University of Massachusetts Medical School https://doi.org/10.13028/j41x-ab26	text	January 2010
Diagnostic Value of Urine Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Acute Kidney Injury: A Meta-Analysis Su, Yuanyuan; Gong, Zhiyan; Wu, Yan PLOS ONE, Vol. 12, Issue 1 https://doi.org/10.1371/journal.pone.0170214	journal	January 2017
Drosophila melanogaster p53 has developmental stage-specific and sex-specific effects on adult life span indicative of sexual antagonistic pleiotropy Waskar, Morris; Landis, Gary N.; Shen, Jie Aging, Vol. 1, Issue 11 https://doi.org/10.18632/aging.100099	journal	October 2009
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Zfra is a small wizard in the mitochondrial apoptosis Dudekula, Subhan; Lee, Ming-Hui; Hsu, Li-Jin Aging, Vol. 2, Issue 12 https://doi.org/10.18632/aging.100263	journal	December 2010
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Nuclear DNA Methylation and Chromatin Condensation Phenotypes Are Distinct Between Normally Proliferating/Aging, Rapidly Growing/Immortal, and Senescent Cells Oh, Jin Ho; Gertych, Arkadiusz; Tajbakhsh, Jian Oncotarget, Vol. 4, Issue 3 https://doi.org/10.18632/oncotarget.942	journal	March 2013
Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR) and Inflammation: Focus on the Gastrointestinal (GI) Tract Spanou, Evagelia; Kalisperati, Polyxeni; Pateras, Ioannis S. Frontiers in Genetics, Vol. 8 https://doi.org/10.3389/fgene.2017.00065	journal	May 2017
With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment Harper, Elizabeth; Sheedy, Emma; Stack, M. Cancers, Vol. 10, Issue 7 https://doi.org/10.3390/cancers10070230	journal	July 2018
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Mechanisms of Radiation Toxicity in Transformed and Non-Transformed Cells Panganiban, Ronald-Allan; Snow, Andrew; Day, Regina International Journal of Molecular Sciences, Vol. 14, Issue 8 https://doi.org/10.3390/ijms140815931	journal	July 2013
A Conformation Variant of p53 Combined with Machine Learning Identifies Alzheimer Disease in Preclinical and Prodromal Stages Abate, Giulia; Vezzoli, Marika; Polito, Letizia Journal of Personalized Medicine, Vol. 11, Issue 1 https://doi.org/10.3390/jpm11010014	journal	December 2020
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Urinary Biomarkers TIMP-2 and IGFBP7 Early Predict Acute Kidney Injury after Major Surgery Göcze, Ivan; Koch, Matthias; Renner, Philipp Universität Regensburg https://doi.org/10.5283/epub.31779	text	January 2015

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