Table of Contents Author Guidelines Submit a Manuscript
Biochemistry Research International
Volume 2012 (2012), Article ID 951574, 8 pages
Review Article

Role of in Replicative Senescence and DNA Damage-Induced Premature Senescence in p53-Deficient Human Cells

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada T6G 1Z2

Received 19 May 2012; Accepted 21 June 2012

Academic Editor: Mandi M. Murph

Copyright © 2012 Razmik Mirzayans et al. 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.


The (hereafter p16) tumor suppressor is encoded by the INK4A/ARF locus which is among the most commonly dysregulated sequences in human cancer. By inhibiting cyclin-dependent kinases, p16 activates the G1-S checkpoint, and this response is often considered to be critical for establishing a senescence-like growth arrest. Not all studies support a universal role for p16 in senescence. Single-cell analysis of noncancerous human fibroblast cultures undergoing senescence as a function of culture age (replicative senescence) has revealed that p16 is not expressed in the majority (>90%) of cells that exhibit features of senescence (e.g., flattened and enlarged morphology coupled with senescence-associated β-galactosidase expression), ruling out a requirement for p16 in this process. In addition, ionizing radiation triggers premature senescence in human cancer cell lines that do not express p16. These observations are made with cells that express wild-type p53, a key mediator of the DNA damage response. In this paper, we examine the growing evidence suggesting a negative regulatory relationship between p16 and p53 and discuss recent reports that implicate a role for p16 in replicative senescence and ionizing radiation-induced premature senescence in human cells that lack wild-type p53 function.