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The polo-like kinase Plx1 prevents premature inactivation of the APCFizzy-dependent pathway in the early Xenopus cell cycle

Abstract

Members of the polo-like family of protein kinases have been involved in the control of APC (anaphase-promoting complex) during the cell cycle, yet how they activate APC is not understood in any detail. In Xenopus oocytes, Ca2+-dependent degradation of cyclin B associated with release from arrest at second meiotic metaphase was demonstrated to require the polo-like kinase Plx1. The aim of the present study was to examine, beyond Ca2+-dependent resumption of meiosis, the possible role of Plx1 in the control of cyclin degradation during the early mitotic cell cycle. Plx1 was found to be dispensable for MPF to turn on the cyclin degradation machinery. However, it is required to prevent premature inactivation of the APC-dependent proteolytic pathway. Microcystin suppresses the requirement for Plx1 in both Ca2+-dependent exit from meiosis, associated with degradation of both cyclin B and A downstream of CaMK2 activation, and prevention of premature APCFizzy inactivation in the early mitotic cell cycle. These results are consistent with the view that Plx1 antagonizes an unidentified microcystin-sensitive phosphatase that inactivates APCFizzy.

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Acknowledgements

We would like to thank P Descombes (University of Geneva, Switzerland) and EA Nigg (Max Planck Institut, Munich, Germany) for the gift of Plx1 proteins and for helpful discussions. We thank Didier Fesquet for critical comments of the manuscript. This work was supported by grants from Association de Recherche contre le Cancer (ARC) for J-C Labbé, the Human Frontier Science Program Organisation (HFSPO) for A Castro and the Ligue Nationale contre le Cancer (LNCC) for T Brassac, T Lorca and S Galas.

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Brassac, T., Castro, A., Lorca, T. et al. The polo-like kinase Plx1 prevents premature inactivation of the APCFizzy-dependent pathway in the early Xenopus cell cycle. Oncogene 19, 3782–3790 (2000). https://doi.org/10.1038/sj.onc.1203724

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