title: Transcriptional targets of p53 that regulate cellular proliferation.
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, targeted 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 type of gene targets may reflect p53-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.
authors.affiliation: Cutaneous Biology Research Center, Massachussetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Brown
authors.forename: Sarah
authors.initials: S
authors.lastname: Boswell
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Raj
authors.forename: Sam W
authors.initials: SW
authors.lastname: Lee
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D051381:Rats; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53