This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bansal, P. Articles by Lazo, J. S. Search for Related Content PubMed PubMed Citation Articles by Bansal, P. Articles by Lazo, J. S.

Induction of Cdc25B Regulates Cell Cycle Resumption after Genotoxic Stress

Department of Pharmacology, University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, Pennsylvania

Requests for reprints: John S. Lazo, Department of Pharmacology, Drug Discovery Institute, Biomedical Science Tower 3, Suite 10040, 3501 Fifth Avenue, University of Pittsburgh, Pittsburgh, PA 15260. Phone: 412-648-9200; Fax: 412-648-9009; E-mail: lazo{at}pitt.edu.

Cdc25 phosphatases propel cell cycle progression by activating cyclin-dependent kinases (Cdk). DNA damage is generally thought to inhibit Cdc25 functionality by inducing proteasomal degradation of Cdc25A and phosphorylation-mediated sequestration of Cdc25B and Cdc25C to the cytoplasm. More recently, a critical role for Cdc25B in the resumption of cell cycle progression through mitosis after DNA damage has been identified. In this study, the fate of Cdc25B after mechanistically distinct DNA-damaging agents (etoposide, cisplatin, bleomycin, ionizing irradiation, or UV irradiation) was examined, and surprisingly a rapid increase in cellular Cdc25B levels was observed after DNA damage. Using UV irradiation as the prototypic damaging agent, we found that the increase in Cdc25B levels was checkpoint dependent and was controlled by a p53-independent mechanism. Cdc25B levels controlled the number of cells progressing into mitosis after UV, but they did not affect G₂-M checkpoint engagement immediately after DNA damage. Increased Cdc25B reduced the time required for cell cycle resumption. These data support a model in which Cdc25B accumulation is an important anticipatory event for cell cycle resumption after DNA damage. [Cancer Res 2007;67(7):3356–63]

This article has been cited by other articles:

				N. G. Thaker, F. Zhang, P. R. McDonald, T. Y. Shun, M. D. Lewen, I. F. Pollack, and J. S. Lazo Identification of Survival Genes in Human Glioblastoma Cells by Small Interfering RNA Screening Mol. Pharmacol., December 1, 2009; 76(6): 1246 - 1255. [Abstract] [Full Text] [PDF]

				H. Wang, X. Zhang, L. Geng, L. Teng, and R. J. Legerski Artemis Regulates Cell Cycle Recovery from the S Phase Checkpoint by Promoting Degradation of Cyclin E J. Biol. Chem., July 3, 2009; 284(27): 18236 - 18243. [Abstract] [Full Text] [PDF]

				R. J. Tomko Jr. and J. S. Lazo Multimodal Control of Cdc25A by Nitrosative Stress Cancer Res., September 15, 2008; 68(18): 7457 - 7465. [Abstract] [Full Text] [PDF]

				S. K. Srivastava, P. Bansal, T. Oguri, J. S. Lazo, and S. V. Singh Cell Division Cycle 25B Phosphatase Is Essential for Benzo(a)Pyrene-7,8-Diol-9,10-Epoxide Induced Neoplastic Transformation Cancer Res., October 1, 2007; 67(19): 9150 - 9157. [Abstract] [Full Text] [PDF]