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

Swastika Sur, Devendra K. Agrawal

    Research output: Contribution to journalReview articlepeer-review

    79 Scopus citations

    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.

    Original languageEnglish
    Pages (from-to)33-46
    Number of pages14
    JournalMolecular and Cellular Biochemistry
    Volume416
    Issue number1-2
    DOIs
    StatePublished - May 1 2016

    All Science Journal Classification (ASJC) codes

    • Clinical Biochemistry
    • Molecular Biology
    • Cell Biology

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