Protein Kinase CK2α’, More than a Backup of CK2α

Abstract

The serine/threonine protein kinase CK2 is implicated in the regulation of fundamental processes in eukaryotic cells. CK2 consists of two catalytic α or α’ isoforms and two regulatory CK2β subunits. These three proteins exist in a free form, bound to other cellular proteins, as tetrameric holoenzymes composed of CK2α2/β2, CK2αα’/β2, or CK2α’2/β2 as well as in higher molecular forms of the tetramers. The catalytic domains of CK2α and CK2α’ share a 90% identity. As CK2α contains a unique C-terminal sequence. Both proteins function as protein kinases. These properties raised the question of whether both isoforms are just backups of each other or whether they are regulated differently and may then function in an isoform-specific manner. The present review provides observations that the regulation of both CK2α isoforms is partly different concerning the subcellular localization, post-translational modifications, and aggregation. Up to now, there are only a few isoform-specific cellular binding partners. The expression of both CK2α isoforms seems to vary in different cell lines, in tissues, in the cell cycle, and with differentiation. There are different reports about the expression and the functions of the CK2α isoforms in tumor cells and tissues. In many cases, a cell-type-specific expression and function is known, which raises the question about cell-specific regulators of both isoforms. Another future challenge is the identification or design of CK2α’-specific inhibitors.

Discovery of a CK2α′-Biased ATP-Competitive Inhibitor from a High-Throughput Screen of an Allosteric-Inhibitor-Like Compound Library

“…This is supported by more than 24,000 studies on PubMed uncovering distinct features and roles of CK2α compared to the only 2,200 studies investigating CK2α′. In addition, only a handful of studies have addressed potential subunit-specific dysregulation or contribution in different diseases in which altered CK2 activity has been reported . Our recent work highlighted the importance of conducting biological studies where the two subunits are investigated.…”

Scoping Pleiotropy of CK2 in Musculoskeletal Disorders for a Novel Targeting Approach

“…However, few substrates are phosphorylated without the β subunit, which makes its role elusive. Fourth, the catalytic subunits CK2α and CK2α' are almost the same in structure, but their involvement in catalytic activity is different [39]. One is preferred over the other in some processes.…”