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Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies

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Abstract

Alterations in the cell-cycle regulatory genes result in uncontrolled cell proliferation leading to several disease conditions. Cyclin-dependent kinases (CDK) and their regulatory subunit, cyclins, are essential proteins in cell-cycle progression. The activity of CDK is regulated by a series of phosphorylation and dephosphorylation at different amino acid residues. Cell Division Cycle-25 (CDC25) plays an important role in transitions between cell-cycle phases by dephosphorylating and activating CDKs. CDC25B and CDC25C play a major role in G2/M progression, whereas CDC25A assists in G1/S transition. Different isomers of CDC25 expressions are upregulated in various clinicopathological situations. Overexpression of CDC25A deregulates G1/S and G2/M events, including the G2 checkpoint. CDC25B has oncogenic properties. Binding to the 14-3-3 proteins regulates the activity and localization of CDC25B. CDC25C is predominantly a nuclear protein in mammalian cells. At the G2/M transition, mitotic activation of CDC25C protein occurs by its dissociation from 14-3-3 proteins along with its phosphorylation at multiple sites within its N-terminal domain. In this article, we critically reviewed the biology of the activation/deactivation of CDC25 by kinases/phosphatases to maintain the level of CDK-cyclin activities and thus the genomic stability, clinical implications due to dysregulation of CDC25, and potential role of CDC25 inhibitors in diseases.

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Acknowledgments

This work was supported by the research grants, R01 HL116042, R01 HL112597, and R01 HL120659 to DK Agrawal from the National Heart, Lung and Blood Institute, the National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with financial interest or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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Correspondence to Devendra K. Agrawal.

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Sur, S., Agrawal, D.K. Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies. Mol Cell Biochem 416, 33–46 (2016). https://doi.org/10.1007/s11010-016-2693-2

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  • DOI: https://doi.org/10.1007/s11010-016-2693-2

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