Inter- and supramolecular interactions of protein kinase CK2 and their relevance for genome integrity

Abstract

CK2 is a pleiotropic and ubiquitous tetrameric serine/threonine protein kinase phosphorylating a plethora of substrates. Beside its typical enzymatic activity, it has been shown that it can undergo stoichiometric (non-enzymatic) interactions with other proteins. This interaction is not only limited to the tetrameric holoenzyme; the individual subunits of CK2, i.e. the catalytic α-subunit and the regulatory β-subunit, can also interact by themselves with other proteins. This is an exciting new development in understanding the structural and physiological role of CK2. We have focused in this overview on this aspect of CK2 function, with emphasis on molecules involved in genome integrity, i.e. p53, MDM2, Chk2, TFIIIB, topoisomerases I/II, Wnt, BRCA1, and APC. Special attention is given to the structural basis within the CK2 molecule, allowing for the discussed interactions in cell lines. We present a model in which the CK2β subunit serves as a docking station for other proteins than only the CK2α subunit, especially here for molecules playing a key role in genome integrity. Our model supports the notion of CK2 and its subunits being possible partners in high molecular mass complexes with dedicated functions known as "osomes" (for details, see below). © 2005 Springer-Verlag Berlin Heidelberg.