Next Article in Journal / Special Issue
The Link between Protein Kinase CK2 and Atypical Kinase Rio1
Previous Article in Journal
Second International Electronic Conference on Medicinal Chemistry (ECMC-2)
Previous Article in Special Issue
CK2 in Cancer: Cellular and Biochemical Mechanisms and Potential Therapeutic Target
Open AccessArticle

In Search of Small Molecule Inhibitors Targeting the Flexible CK2 Subunit Interface

Biology of Cancer and Infection, INSERM, U 1036, 38054 Grenoble, France
Biology of Cancer and Infection, University Grenoble-Alpes (UGA), 38000 Grenoble, France
Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Direction de Recherche Fondamentale (DRF), Biosciences and Biotechnology Institute of Grenoble (BIG), Biology of Cancer and Infection (BCI), 38054 Grenoble, France
Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany
Faculté de Pharmacie—ISPB, EA 4446 Bioactive Molecules and Medicinal Chemistry, SFR Santé Lyon-Est CNRS UMS3453—INSERM US7 Université Lyon 1, 8 avenue Rockefeller, F-69373 Lyon CEDEX 8, France
INSERM U 1163 / CNRS ERL 8254, Institut IMAGINE, Université Paris Descartes, 75015 Paris, France
Author to whom correspondence should be addressed.
Academic Editor: Joachim Jose
Pharmaceuticals 2017, 10(1), 16;
Received: 25 November 2016 / Revised: 16 January 2017 / Accepted: 22 January 2017 / Published: 3 February 2017
Protein kinase CK2 is a tetrameric holoenzyme composed of two catalytic (α and/or α’) subunits and two regulatory (β) subunits. Crystallographic data paired with fluorescence imaging techniques have suggested that the formation of the CK2 holoenzyme complex within cells is a dynamic process. Although the monomeric CK2α subunit is endowed with a constitutive catalytic activity, many of the plethora of CK2 substrates are exclusively phosphorylated by the CK2 holoenzyme. This means that the spatial and high affinity interaction between CK2α and CK2β subunits is critically important and that its disruption may provide a powerful and selective way to block the phosphorylation of substrates requiring the presence of CK2β. In search of compounds inhibiting this critical protein–protein interaction, we previously designed an active cyclic peptide (Pc) derived from the CK2β carboxy-terminal domain that can efficiently antagonize the CK2 subunit interaction. To understand the functional significance of this interaction, we generated cell-permeable versions of Pc, exploring its molecular mechanisms of action and the perturbations of the signaling pathways that it induces in intact cells. The identification of small molecules inhibitors of this critical interaction may represent the first-choice approach to manipulate CK2 in an unconventional way. View Full-Text
Keywords: protein kinase CK2; subunit interface; cyclic peptides; protein–protein interaction; cell death protein kinase CK2; subunit interface; cyclic peptides; protein–protein interaction; cell death
Show Figures

Figure 1

MDPI and ACS Style

Bestgen, B.; Belaid-Choucair, Z.; Lomberget, T.; Le Borgne, M.; Filhol, O.; Cochet, C. In Search of Small Molecule Inhibitors Targeting the Flexible CK2 Subunit Interface. Pharmaceuticals 2017, 10, 16.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Search more from Scilit
Back to TopTop