Many fingers on the mitotic trigger: Post-translational regulation of the Cdc25C phosphatase

James R A Hutchins, Paul R. Clarke

    Research output: Contribution to journalReview articlepeer-review

    62 Citations (Scopus)

    Abstract

    The mitotic inducer Cdc25 phosphatase controls the activation of Cdc2/cyclin B protein kinase and entry into mitosis in eukaryotic cells. Cdc25C is highly regulated by multiple post-translational modifications within its N-terminal regulatory domain and site-specific protein interactions. Phosphorylation of one inhibitory site targeted by multiple kinases determines the timing of Cdc25C activation and arrests cells in G2 in response to checkpoint, stress, developmental and extracellular signals. In mitosis, phosphorylation of several Ser/Thr residues and Pin1-catalysed peptidyl-proline isomerisation produces activation. Phosphorylation of one activating site is antagonistic to the proximal inhibitory site and maintains Cdc25C activity during mitosis. Phosphorylation and interacting proteins also modulate the nuclear import and export signals on Cdc25C, inducing dramatic changes in its localization within the cell. Thus, the regulation of Cdc25C activity and localisation integrates multiple signals that govern the decision to enter mitosis.

    Original languageEnglish
    Pages (from-to)41-45
    Number of pages5
    JournalCell Cycle
    Volume3
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2004

    Keywords

    • 14-3-3
    • CaMKII
    • Cds1/Chk2
    • Cell cycle checkpoint
    • Cellular stress
    • Chk1
    • Mitosis
    • Pin1
    • Polo

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology
    • Cell Biology

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