Protein kinase CK2-A key suppressor of apoptosis

Protein kinase CK2 is a ubiquitous and highly conserved protein serine/threonine kinase that is indispensable for cell survival. CK2 has long been implicated in cell growth and proliferation, and studies from several laboratories have suggested that CK2 plays a global role in affecting cell growth related activities. Recently, we documented that CK2, besides its role in cell growth and proliferation, can potently suppress apoptosis. Considering that CK2 has been found to be elevated in all the cancers that have been examined, the ability of CK2 to suppress apoptosis is particularly important in the context of cancer cell pathobiology since these cells exhibit dysregulation of both cell proliferation and cell death. Thus, overexpression of CK2 in cancer cells may impart a survival advantage by its action as a suppressor of apoptotic activity in these cells while promoting cell growth. In experimental studies, we have shown that overexpression of CK2 in cells can potently inhibit apoptosis mediated by a variety of agents including removal of survival factors, chemical and physical agents, and death receptor ligands. On the other hand, inhibition of CK2 by chemical inhibitors or by its molecular downregulation by antisense CK2 ODN or siRNA leads to potent induction of apoptosis. Downregulation of CK2 is associated with apoptosis mediated via effects on several downstream targets, and it appears that CK2 may have a global impact on the apoptotic machinery. While CK2 is present in both the nuclear and cytoplasmic compartments, several of its cell growth and cell death related activities appear to be associated with its signalling to the nuclear structures such as chromatin and nuclear matrix. In general, shuttling of CK2 to these compartments correlates with its role in cell growth and suppression of apoptotic activity whereas loss of CK2 from the nuclear structures is associated with induction of apoptosis and cessation of cell growth. These various observations on the biology of CK2 have led to our original proposal that CK2 is a potentially important target for cancer chemopreventive and therapeutic approaches; this is now being substantiated by recent studies.