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Differential mitotic degradation of the CDC25B phosphatase variants

Oncogene volume 26, pages 7847–7858 (2007)Cite this article

Abstract

CDC25 phosphatases control cell-cycle progression by dephosphorylating and activating cyclin-dependent kinases. CDC25B, one of the three members of this family in human cells, is thought to regulate initial mitotic events. CDC25B is an unstable protein whose proteasomal degradation is proposed to be controlled by β-TrCP. Here, we have investigated the regulation of CDC25B during mitosis, using time-lapse video microscopy. We found that CDC25B expression is high during early mitosis, and that its degradation occurs after the metaphase–anaphase transition and cyclin B1 destruction. We also show that CDC25B degradation after metaphase is dependent on the integrity of the KEN-box and RRKSE motifs that are located within the alternatively spliced B domain, and that the CDC25B2 splice variant, that lacks this domain, is stable during mitosis. Furthermore, we show that the N-terminal region of CDC25B, encompassing the B domain, undergoes major conformational changes during mitosis that can be monitored by intramolecular fluorescence resonance energy transfer variation of specific CDC25B biosensors. This study demonstrates that CDC25B splice variants have differential mitotic stabilities, a feature that is likely to have major consequences on the local control of cyclin-dependent kinase–cyclin activities during mitotic progression.

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Acknowledgements

We gratefully acknowledge Rose Boutros for comments and suggestions on the manuscript, Martine Cazales and Christine Didier for help and technical support. We thank R Tsien, W Earnshaw and D Piston for plasmids and reagents. This work was supported by the CNRS, l'Université Paul Sabatier and la Ligue Nationale Contre le Cancer to BD (Equipe labellisée 2005).

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Author notes

  1. I Kieffer and C Lorenzo: These authors contributed equally to this work.

Authors and Affiliations

  1. LBCMCP-CNRS UMR5088- IFR109 ‘Institut d'Exploration Fonctionnelle des Génomes’, Université Paul Sabatier, 118 route de Narbonne, Toulouse, France

    I Kieffer, C Lorenzo, C Dozier, E Schmitt & B Ducommun

  2. CHU Purpan, TSA 40031, Toulouse Cedex, France

    B Ducommun

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  1. I Kieffer
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  2. C Lorenzo
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  3. C Dozier
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  4. E Schmitt
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Correspondence to B Ducommun.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Kieffer, I., Lorenzo, C., Dozier, C. et al. Differential mitotic degradation of the CDC25B phosphatase variants. Oncogene 26, 7847–7858 (2007). https://doi.org/10.1038/sj.onc.1210596

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