The regulated assembly of a PKC epsilon complex controls the completion of cytokinesis

Adrian T. Saurin (Lead / Corresponding author), Joanne Durgan, Angus J. Cameron, Amir Faisal, Michael S. Marber, Peter J. Parker (Lead / Corresponding author)

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    84 Citations (Scopus)

    Abstract

    The cell cycle is exquisitely controlled by multiple sequential regulatory inputs to ensure fidelity. Here we demonstrate that the final step in division, the physical separation of daughter cells, is controlled by a member of the PKC gene superfamily. Specifically, we have identified three phosphorylation sites within PKC epsilon that control its association with 14-3-3. These phosphorylations are executed by p38 MAP kinase (Ser 350), GSK3 (Ser 346) and PKC itself (Ser 368). Integration of these signals is essential during mitosis because mutations that prevent phosphorylation of PKC epsilon and/or PKC epsilon binding to 14-3-3 also cause defects in the completion of cytokinesis. Using chemical genetic and dominant-negative approaches it is shown that selective inhibition of PKCe halts cells at the final stages of separation. This arrest is associated with persistent RhoA activation at the midbody and a delay in actomyosin ring dissociation. This study therefore identifies a new regulatory mechanism that controls exit from cytokinesis, which has implications for carcinogenesis.

    Original languageEnglish
    Pages (from-to)891-901
    Number of pages11
    JournalNature Cell Biology
    Volume10
    Issue number8
    DOIs
    Publication statusPublished - Aug 2008

    Keywords

    • BINDING
    • PROTEIN-KINASE-C
    • IDENTIFICATION
    • PHOSPHORYLATION
    • CELLS
    • CLEAVAGE FURROW
    • CONTRACTILE RING
    • STRUCTURAL BASIS
    • SPECIFICITY
    • TUMORIGENESIS

    Cite this

    Saurin, A. T., Durgan, J., Cameron, A. J., Faisal, A., Marber, M. S., & Parker, P. J. (2008). The regulated assembly of a PKC epsilon complex controls the completion of cytokinesis. Nature Cell Biology, 10(8), 891-901. https://doi.org/10.1038/ncb1749