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Molecular and Cellular Biology, April 2009, p. 2068-2081, Vol. 29, No. 8
0270-7306/09/$08.00+0     doi:10.1128/MCB.01563-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Evidence for Regulation of Mitotic Progression through Temporal Phosphorylation and Dephosphorylation of CK2{alpha}{triangledown} ,{dagger}

Nicole A. St-Denis,1,{ddagger} D. Richard Derksen,1,{ddagger} and David W. Litchfield1,2*

Departments of Biochemistry,1 Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C12

Received 6 October 2008/ Returned for modification 2 December 2008/ Accepted 23 January 2009

Proper mitotic progression is crucial for maintenance of genomic integrity in proliferating cells and is regulated through an intricate series of events, including protein phosphorylation governed by a complex network of protein kinases. One kinase family implicated in the regulation of mitotic progression is protein kinase CK2, a small family of enzymes that is overexpressed in cancer and induces transformation in mice and cultured fibroblasts. CK2{alpha}, one isoform of the catalytic subunits of CK2, is maximally phosphorylated at four sites in nocodazole-treated cells. To investigate the effects of CK2{alpha} phosphorylation on mitotic progression, we generated phosphospecific antibodies against its mitotic phosphorylation sites. In U2OS cells released from S-phase arrest, these antibodies reveal that CK2{alpha} is most highly phosphorylated in prophase and metaphase. Phosphorylation gradually decreases during anaphase and becomes undetectable during telophase and cytokinesis. Stable expression of phosphomimetic CK2{alpha} (CK2{alpha}-4D, CK2{alpha}-4E) results in aberrant centrosome amplification and chromosomal segregation defects and loss of mitotic cells through mitotic catastrophe. Conversely, cells expressing nonphosphorylatable CK2{alpha} (CK2{alpha}-4A) show a decreased ability to arrest in mitosis following nocodazole treatment, suggesting involvement in the spindle assembly checkpoint. Collectively, these studies indicate that reversible phosphorylation of CK2{alpha} requires precise regulation to allow proper mitotic progression.

* Corresponding author. Mailing address: Department of Biochemistry, Medical Sciences Building, University of Western Ontario, London, Ontario, Canada N6A 5C1. Phone: (519) 661-4186. Fax: (519) 661-3175. E-mail: litchfi{at}uwo.ca

{triangledown} Published ahead of print on 2 February 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this report.

Molecular and Cellular Biology, April 2009, p. 2068-2081, Vol. 29, No. 8
0270-7306/09/$08.00+0     doi:10.1128/MCB.01563-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, D., Jang, D.-J. (2009). Protein Kinase CK2 Regulates Cytoskeletal Reorganization during Ionizing Radiation-Induced Senescence of Human Mesenchymal Stem Cells. Cancer Res. 69: 8200-8207 [Abstract] [Full Text]  


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