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  • Original Paper
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Phosphorylation regulates the stability of the regulatory CK2β subunit

Oncogene volume 21, pages 3754–3764 (2002)Cite this article

Abstract

Protein kinase CK2 is a protein serine/threonine kinase that exhibits elevated expression in a number of cancers and displays oncogenic activity in mice. The regulatory CK2β subunit has a central role in assembly of functional tetrameric CK2 complexes where it participates in modulation of catalytic activity and substrate specificity. Since overexpression of CK2β results in elevated levels of CK2 activity, we investigated the molecular mechanisms that control its degradation since perturbations in these pathways could contribute to elevated CK2 in cancer. In this study, we demonstrate that CK2β is degraded by a proteasome-dependent pathway and that it is ubiquitinated. We have also investigated the role of phosphorylation and a putative destruction box in regulating its stability in cells. Importantly, replacement of three serine residues within the autophosphorylation site of CK2β with glutamic acid residues resulted in a significant decrease in its degradation indicating that autophosphorylation is involved in regulating its stability. Notably, although the autophosphorylation site of CK2β is remarkably conserved between species, this is the first functional role ascribed to this site. Furthermore, based on these results, we speculate that alterations in the phosphorylation or dephosphorylation of the regulatory CK2β subunit could underlie the elevated expression of CK2 that is observed in cancer cells.

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Acknowledgements

We are grateful to Kevin Graham and Rebecca St. Pierre for plasmid construction and optimization of procedures required for the ubiquitination assays. We are also grateful to Drs Chris Brandl and Eric Ball for helpful discussion, to Drs Daniela Rotin (Toronto, Canada) and Dirk Bohmann (Heidelberg, Germany) for providing plasmids and to Dr Lina Dagnino for supplying anti-β-tubulin antibodies. The 9E10 monoclonal antibody developed by JM Bishop was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. This work was supported by the National Cancer Institute of Canada with funds from the Canadian Cancer Society and from the Canadian Institutes of Health Research (to DW Litchfield). Cunjie Zhang was supported in part by the Premier's Research Excellence Award program (Ontario, Canada). Greg Vilk is the recipient of a Studentship from the National Cancer Institute of Canada and David Canton is supported by a Scholarship from the Natural Sciences and Engineering Research Council of Canada.

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  1. Department of Biochemistry, University of Western Ontario, London, N6A 5C1, Ontario, Canada

    Cunjie Zhang, Greg Vilk, David A Canton & David W Litchfield

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  1. Cunjie Zhang
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Correspondence to David W Litchfield.

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Zhang, C., Vilk, G., Canton, D. et al. Phosphorylation regulates the stability of the regulatory CK2β subunit. Oncogene 21, 3754–3764 (2002). https://doi.org/10.1038/sj.onc.1205467

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