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Regulation of DNA-dependent protein kinase by protein kinase CK2 in human glioblastoma cells

Oncogene volume 29, pages 6016–6026 (2010)Cite this article

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Abstract

The DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase composed of a large catalytic subunit (DNA-PKcs) and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the nonhomologous end-joining pathway of DNA double-strand breaks repair. Although DNA-PK has been biochemically characterized in vitro, relatively little is known about its functions in the context of DNA repair and how its kinase activity is precisely regulated in vivo. Here, we report that cellular depletion of the individual catalytic subunits of protein kinase CK2 by RNA interference leads to significant cell death in M059K human glioblastoma cells expressing DNA-PKcs, but not in their isogenic counterpart, that is M059J cells, devoid of DNA-PKcs. The lack of CK2 results in enhanced DNA-PKcs activity and strongly inhibits DNA damage-induced autophosphorylation of DNA-PKcs at S2056 as well as repair of DNA double-strand breaks. By the application of the in situ proximity ligation assay, we show that CK2 interacts with DNA-PKcs in normal growing cells and that the association increases upon DNA damage. These results indicate that CK2 has an important role in the modulation of DNA-PKcs activity and its phosphorylation status providing important insights into the mechanisms by which DNA-PKcs is regulated in vivo.

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Acknowledgements

This study was supported by grants from the Danish Cancer Society (DP08152) and the Danish Natural Science Research Council (272–07–0258) to BG. BBO and OGI were supported by grants from the Danish Cancer Society (DP06083, DP07109).

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Authors and Affiliations

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

    B B Olsen, O-G Issinger & B Guerra

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  1. B B Olsen
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  2. O-G Issinger
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  3. B Guerra
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Correspondence to B Guerra.

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Olsen, B., Issinger, OG. & Guerra, B. Regulation of DNA-dependent protein kinase by protein kinase CK2 in human glioblastoma cells. Oncogene 29, 6016–6026 (2010). https://doi.org/10.1038/onc.2010.337

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