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Coupling of Polo kinase activation to nuclear localization by a bifunctional NLS is required during mitotic entry

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  • David Kachaner

    (Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128 Succursale Centre-Ville
    Université de Montréal, C.P. 6128 Succursale Centre-Ville)

  • Damien Garrido

    (Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128 Succursale Centre-Ville
    Université de Montréal, C.P. 6128 Succursale Centre-Ville)

  • Haytham Mehsen

    (Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128 Succursale Centre-Ville)

  • Karine Normandin

    (Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128 Succursale Centre-Ville)

  • Hugo Lavoie

    (Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128 Succursale Centre-Ville)

  • Vincent Archambault

    (Institute for Research in Immunology and Cancer, Université de Montréal, C.P. 6128 Succursale Centre-Ville
    Université de Montréal, C.P. 6128 Succursale Centre-Ville)

Abstract

The Polo kinase is a master regulator of mitosis and cytokinesis conserved from yeasts to humans. Polo is composed of an N-term kinase domain (KD) and a C-term polo-box domain (PBD), which regulates its subcellular localizations. The PBD and KD can interact and inhibit each other, and this reciprocal inhibition is relieved when Polo is phosphorylated at its activation loop. How Polo activation and localization are coupled during mitotic entry is unknown. Here we report that PBD binding to the KD masks a nuclear localization signal (NLS). Activating phosphorylation of the KD leads to exposure of the NLS and entry of Polo into the nucleus before nuclear envelope breakdown. Failures of this mechanism result in misregulation of the Cdk1-activating Cdc25 phosphatase and lead to mitotic and developmental defects in Drosophila. These results uncover spatiotemporal mechanisms linking master regulatory enzymes during mitotic entry.

Suggested Citation

  • David Kachaner & Damien Garrido & Haytham Mehsen & Karine Normandin & Hugo Lavoie & Vincent Archambault, 2017. "Coupling of Polo kinase activation to nuclear localization by a bifunctional NLS is required during mitotic entry," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01876-8
    DOI: 10.1038/s41467-017-01876-8
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    Cited by:

    1. Shuo Yang & Jennifer McAdow & Yingqiu Du & Jennifer Trigg & Paul H. Taghert & Aaron N. Johnson, 2022. "Spatiotemporal expression of regulatory kinases directs the transition from mitosis to cellular morphogenesis in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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