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p53 downregulates expression of the G1/S cell cycle phosphatase Cdc25A

Oncogene volume 26, pages 1949–1953 (2007)Cite this article

Abstract

Overexpression of Cdc25A phosphatase is often observed in cancer and results in poor prognosis. Cdc25A mainly dephosphorylates and thereby activates Cyclin-dependent kinase 2 and thus induces progression in the cell cycle from G1 to S phase. Here, we demonstrate that the tumor suppressor p53 downregulates expression from the Cdc25A gene. In a p53-inducible cell system, Cdc25A expression on the mRNA and protein level is downregulated upon p53 expression. Promoter-reporter assays show that this regulation is dependent on the Cdc25A promoter. Mutant p53 fails to reduce Cdc25A transcription. In contrast to p53, neither p63 nor p73 can repress Cdc25A transcription. The Cdc25A promoter displays no p53 binding site, and p53 does not bind directly to the promoter DNA as shown by chromatin immunoprecipitation assays. Previously, the contribution of p53 to G1/S arrest has been mostly linked to activating the expression of the Cdk inhibitor p21WAF1/CIP1. By downregulating Cdc25A expression, p53 may impair transition from G1 to S phase independently of p21WAF1/CIP1. Therefore, the data suggest that, as long as p53 is intact, Cdc25A transcriptional downregulation might play a role in cancer prevention.

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Acknowledgements

We thank Bert Vogelstein for providing plasmids and cells, Ingrid Hoffmann for the Cdc25A cDNA and an antibody preparation, Jana Lorenz for expert technical assistance and Christine Engeland for critical reading of the paper. This work was supported by grants from the Interdisziplinäres Zentrum für Klinische Forschung (IZKF) Leipzig and the Deutsche Forschungsgemeinschaft (to KE).

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  1. Medizinische Klinik und Poliklinik II, Max-Bürger-Forschungszentrum, Universität Leipzig, Leipzig, Germany

    K Rother, R Kirschner, K Sänger, L Böhlig, J Mössner & K Engeland

  2. Interdisziplinäres Zentrum für Klinische Forschung (IZKF) Leipzig, Max-Bürger-Forschungszentrum, Universität Leipzig, Leipzig, Germany

    K Rother & L Böhlig

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  1. K Rother
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Correspondence to K Engeland.

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Rother, K., Kirschner, R., Sänger, K. et al. p53 downregulates expression of the G1/S cell cycle phosphatase Cdc25A. Oncogene 26, 1949–1953 (2007). https://doi.org/10.1038/sj.onc.1209989

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