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Molecular and Cellular Biology, April 2002, p. 2441-2449, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2441-2449.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mutation of Mouse p53 Ser23 and the Response to DNA Damage

Zhiqun Wu,1 John Earle,1 Shin'ichi Saito,2 Carl W. Anderson,3 Ettore Appella,2 and Yang Xu1*

Section of Molecular Biology, Division of Biology, University of California, San Diego, La Jolla, California 92093-0322,1 Laboratory of Cell Biology, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892 ,2 Biology Department, Brookhaven National Laboratory, Upton, New York 119733

Received 15 June 2001/ Returned for modification 8 August 2001/ Accepted 15 January 2002

Recent studies have suggested that phosphorylation of human p53 at Ser20 is important for stabilizing p53 in response to DNA damage through disruption of the interaction between MDM2 and p53. To examine the requirement for this DNA damage-induced phosphorylation event in a more physiological setting, we introduced a missense mutation into the endogenous p53 gene of mouse embryonic stem (ES) cells that changes serine 23 (S23), the murine equivalent of human serine 20, to alanine (A). Murine embryonic fibroblasts harboring the p53S23A mutation accumulate p53 as well as p21 and Mdm2 proteins to normal levels after DNA damage. Furthermore, ES cells and thymocytes harboring the p53S23A mutation also accumulate p53 protein to wild-type levels and undergo p53-dependent apoptosis similarly to wild-type cells after DNA damage. Therefore, phosphorylation of murine p53 at Ser23 is not required for p53 responses to DNA damage induced by UV and ionizing radiation treatment.

* Corresponding author. Mailing address: Division of Biology, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0322. Phone: (858) 822-1084. Fax: (858) 534-0053. E-mail: yangxu{at}ucsd.edu.

Molecular and Cellular Biology, April 2002, p. 2441-2449, Vol. 22, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.8.2441-2449.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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