Identification of chemical inhibitors of protein-kinase CK2 subunit interaction.
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. CK2beta-derived cyclopeptides that target a well-defined hydrophobic pocket on CK2alpha 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 CK2alpha/CK2beta interface inducing selective disruption of the CK2alpha/CK2beta assembly and concomitant inhibition of CK2alpha activity.
INSERM, U873, Grenoble, 38054, France.
Béatrice
B
Laudet
Virginie
V
Moucadel
Renaud
R
Prudent
Odile
O
Filhol
Yung-Sing
YS
Wong
Daniel
D
Royer
Claude
C
Cochet
D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D002384:Catalysis / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D021122:Protein Subunits / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D047390:Casein Kinase II