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Review
. 2012 Jul;12(6):631-9.
doi: 10.2174/187152012800617678.

The role of Cdc25A in the regulation of cell proliferation and apoptosis

Tao Shen  1 , Shile Huang
Affiliations
Review

The role of Cdc25A in the regulation of cell proliferation and apoptosis

Tao Shen et al. Anticancer Agents Med Chem. 2012 Jul.

Abstract

Cell division cycle 25 A (Cdc25A), a dual-specificity protein phosphatase, is one of the most crucial cell cycle regulators, which removes the inhibitory phosphorylation in cyclin-dependent kinases (CDKs), such as CDK2, CDK4, and CDK6, and positively regulates the activities of CDKs that lead to cell cycle progression. In addition, Cdc25A also acts as a regulator of apoptosis. Overexpression of Cdc25A promotes tumorigenesis, and is frequently observed in various types of cancer. Here we briefly summarize current understanding of the role of Cdc25A in cell proliferation and apoptosis, as well as the impact of overexpression of Cdc25A on tumorigenesis.

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Figures

Fig. (1)
Fig. (1)
Promotion of G1/S transition by Cdc25A. Cdc25A activates cyclin D-CDK4 complex and cyclin E-CDK2 complex, which phosphorylate Rb and dissociate Rb from complex with E2F1, releasing inhibition on E2F1, whose activity is essential for G1/S transition.
Fig. (2)
Fig. (2)
Regulation of Cdc25A in response of genotoxic stress. Upon DNA damage, p53 and ATR/ATM machinery are activated individually. Activated p53 inhibits Cdc25A transcription through ATF3 activation, and activated ATR/ATM promotes Cdc25A turnover through checkpoint activation.
Fig. (3)
Fig. (3)
Regulation of G2/M transition by Cdc25A. Cdc25B initiates CDK1 activity by dephosphorylating p-T14/Y15 on CDK1. Activated CDK1 stabilizes Cdc25A by phosphorylating at S17/S115 on Cdc25A, which can feedforwardly elevate CDK1 activity by removing inhibitory phosphorylation on CDK1. The feedforward loop between CDK1 and Cdc25A is critical for G2/M transition.
Fig. (4)
Fig. (4)
Inhibition of ASK1 activation and apoptosis by Cdc25A. Cdc25A inhibits ASK1 activity by binding to ASK1 and interrupting ASK1 oligomer formation, thus preventing cell apoptosis.
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References

    1. Sherr CJ. Cancer cell cycles. Science. 1996;274:1672–1677. - PubMed
    1. Evan G, Vousden K. Proliferation, cell cycle and apoptosis in cancer. Nature. 2001;411:342–348. - PubMed
    1. Croce C. Oncogenes and cancer. N. Engl. J. Med. 2008;358:502–511. - PubMed
    1. Golias C, Charalabopoulos A, Charalabopoulos K. Cell proliferation and cell cycle control: a mini review. Int. J. Clin. Pract. 2004;58:1134–1141. - PubMed
    1. Vermeulen K, Van Bockstaele D, Berneman Z. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36:131–149. - PMC - PubMed

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