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Critical Reviews™ in Eukaryotic Gene Expression
IF: 1.841 5-Year IF: 1.927 SJR: 0.649 SNIP: 0.516 CiteScore™: 1.96

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v17.i1.50
pages 73-86

Transcriptional Targets of p53 That Regulate Cellular Proliferation

Lauren Brown
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129
Sarah Boswell
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129
Lakshmi Raj
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129
Sam W. Lee
Cutaneous Biology Research Center, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129

ABSTRACT

In response to various forms of cellular stress, including DNA damage, ribonucleotide depletion, and abnormal proliferative signals, p53 becomes activated as a transcription factor, targeting genes that induce cell-cycle arrest and apoptosis. Eliminating damaged, stressed, or abnormally proliferating cells from the replicating cell population prevents the propagation of potentially cancer-prone cells. Here we focus on the transcriptional targets of p53 that regulate the cell cycle. p53 induction of G1/S cell-cycle arrest is largely attributed to the transcriptional upregulation of p21WAF1, and more recently, to the transcriptional repression of c-MYC. The role of p53 in G2/M cell-cycle arrest in response to DNA damage is more complex, involving multiple targets that can generally be considered to impinge upon either the cell cycle (e.g., Cyclin-B, cdc2, cdc25C) or the mitotic machinery (i.e., Topoisomerase II, B99/Gtse-1, and MAP4). The ability of p53 to regulate these two types of gene targets may reflectp53-mediated early versus late events in the G2/M cell-cycle arrest response. Together the information presented illustrates the need for further studies to precisely delineate the nature of G2/M cell-cycle arrest in response to cell stress, and defines the role of p53 in what is likely an important mechanism of tumor suppression.


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