Nucleic Acids Research Advance Access originally published online on October 16, 2007
Nucleic Acids Research 2007 35(22):7475-7484; doi:10.1093/nar/gkm744
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Nucleic Acids Research, 2007, Vol. 35, No. 22 7475-7484
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Two faces of p53: aging and tumor suppression
1Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945 and 2Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
* To whom correspondence should be addressed. Tel: +1 415 209 2042; Fax: 415-209-22232; Email: dbhaumik{at}buckinstitute.org
Received July 12, 2007. Revised September 5, 2007. Accepted September 5, 2007.
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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