Abstract
Protein kinase CK2 is a multi-subunit complex whose dynamic assembly appears as a crucial point of regulation. The ability to interfere with specific protein–protein interactions has already provided powerful means of influencing the functions of selected proteins within the cell. CK2β-derived cyclopeptides that target a well-defined hydrophobic pocket on CK2α have been previously characterized as potent inhibitors of CK2 subunit assembly [9]. As a first step toward the rational design of low molecular weight CK2 antagonists, we have in the present study screened a collection of podophyllotoxine indolo-analogues to identify chemical inhibitors of the CK2 subunit interaction. We report the identification of a podophyllotoxine indolo-analogue as a chemical ligand that binds to the CK2α/CK2β interface inducing selective disruption of the CK2α/CK2β assembly and concomitant inhibition of CK2α activity.
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Acknowledgments
This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Commissariat à l’Energie Atomique (CEA), the Ligue Nationale contre le Cancer (Equipe labellisée 2007), and the Institut National du Cancer (grant no. 57) and by the Centre National pour la Recherche Scientifique (CNRS) and the Université Joseph Fourier (UJF).
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Laudet, B., Moucadel, V., Prudent, R. et al. Identification of chemical inhibitors of protein-kinase CK2 subunit interaction. Mol Cell Biochem 316, 63–69 (2008). https://doi.org/10.1007/s11010-008-9821-6
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DOI: https://doi.org/10.1007/s11010-008-9821-6