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Molecular and Cellular Biology, April 2005, p. 2853-2860, Vol. 25, No. 7
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.7.2853-2860.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Normal Cell Cycle and Checkpoint Responses in Mice and Cells Lacking Cdc25B and Cdc25C Protein Phosphatases

Angela M. Ferguson,1 Lynn S. White,2 Peter J. Donovan,3,4 and Helen Piwnica-Worms1,2,5*

Department of Cell Biology and Physiology,1 Howard Hughes Medical Institute,2 Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri,5 Department of Obstetrics and Gynecology,3 Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland4

Received 1 October 2004/ Returned for modification 10 December 2004/ Accepted 7 January 2005

The Cdc25 family of protein phosphatases positively regulates cell division by activating cyclin-dependent protein kinases (CDKs). In humans and rodents, there are three Cdc25 family members—denoted Cdc25A, Cdc25B, and Cdc25C—that can be distinguished based on their subcellular compartmentalizations, their abundances and/or activities throughout the cell cycle, the CDKs that they target for activation, and whether they are overexpressed in human cancers. In addition, murine forms of Cdc25 exhibit distinct patterns of expression throughout development and in adult tissues. These properties suggest that individual Cdc25 family members contribute distinct biological functions in embryonic and adult cell cycles of mammals. Interestingly, mice with Cdc25C disrupted are healthy, and cells derived from these mice exhibit normal cell cycles and checkpoint responses. Cdc25B–/– mice are also generally normal (although females are sterile), and cells derived from Cdc25B–/– mice have normal cell cycles. Here we report that mice lacking both Cdc25B and Cdc25C are obtained at the expected Mendelian ratios, indicating that Cdc25B and Cdc25C are not required for mouse development or mitotic entry. Furthermore, cell cycles, DNA damage responses, and Cdc25A regulation are normal in cells lacking Cdc25B and Cdc25C. These findings indicate that Cdc25A, or possibly other phosphatases, is able to functionally compensate for the loss of Cdc25B and Cdc25C in mice.

* Corresponding author. Mailing address: Department of Cell Biology and Physiology & Howard Hughes Medical Institute, Washington University School of Medicine, Box 8228, 660 South Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-6812. Fax: (314) 362-3709. E-mail: hpiwnica{at}cellbio.wustl.edu.

Molecular and Cellular Biology, April 2005, p. 2853-2860, Vol. 25, No. 7
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.7.2853-2860.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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