Protein Kinase CK2 in Health and Disease

Abstract.

CK2 is a highly conserved tetrameric serine/ threonine kinase present in all eukaryotic organisms. It is constitutively active, and appears to be regulated by level of expression and activity, and subcellular localization. In turn, it has been postulated to control the function of many proteins through changes in phosphorylation that affect protein stability, protein-protein interactions, and subcellular localization. Through these mechanisms, CK2 regulates many fundamental cellular properties. An enzyme that carries out such a master regulatory function is likely to be important in organismic development and in cancer. We have shown that overexpression of CK2 catalytic subunits is capable of promoting tumorigenesis, and that loss of CK2 catalytic subunits in development can be lethal. Through studies in cells, mice, and frogs, we and others have identified the Wnt and NF-κB pathways as two key signal transduction pathways that are regulated by CK2 activity, in embryonic development and in cancer. These results suggest that inhibiting CK2 could be useful in treating cancer, but dangerous to developing organisms.