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The regulatory β-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis

Oncogene volume 27, pages 4986–4997 (2008)Cite this article

Abstract

Cell-cycle transition from the G2 phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC25 dual-specificity phosphatase family members. In somatic cells, Wee1 is downregulated by phosphorylation and ubiquitin-mediated degradation to ensure rapid activation of CDK1 at the beginning of M phase. Here, we show that downregulation of the regulatory β-subunit of protein kinase CK2 by RNA interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2β causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1–Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found that CK2β participates in PLK1–Wee1 complex formation whereas its cellular depletion leads to disruption of PLK1–Wee1 interaction and reduced Wee1 phosphorylation at Ser53 and 121. The data reported here reinforce the notion that CK2β has functions that are independent of its role as the CK2 regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.

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Acknowledgements

We thank T Holm for technical assistance. This study was supported by the Novo Nordisk Foundation, grant no. 5373 and the Danish Medical Research Council, grant no. 271-07-0464 to BG.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark

    C W Yde, B B Olsen & B Guerra

  2. Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

    D Meek

  3. Antibiotics Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama, Japan

    N Watanabe

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  1. C W Yde
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  2. B B Olsen
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  3. D Meek
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  4. N Watanabe
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  5. B Guerra
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Correspondence to B Guerra.

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Yde, C., Olsen, B., Meek, D. et al. The regulatory β-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis. Oncogene 27, 4986–4997 (2008). https://doi.org/10.1038/onc.2008.146

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