Cell cycle dependent regulation of protein kinase CK2 signaling to the nuclear matrix

Abstract

Protein kinase CK2 is a ubiquitous protein serine/threonine kinase that is involved in cell growth and proliferation as well as suppression of apoptosis. Several studies have suggested that the kinase plays a role in cell cycle progression; however, changes in enzyme activity during phases of cell cycle have not been detected. Nuclear matrix is a key locus for CK2 signaling in the nucleus. We therefore examined CK2 signaling to the nuclear matrix in distinct phases of cell cycle by employing synchronized ALVA-41 prostate cancer cells. Removal of serum from the culture medium resulted in G0/G1 arrest, and a reduction in the nuclear matrix-associated CK2 activity which was rapidly reversed on addition of serum. Arresting the cells in G(0)/G(1) phase with hydroxyurea and subsequent release to S phase by serum gave similar results. Cells arrested in the G(2)/M phase by treatment with nocodazole demonstrated an extensive reduction in the nuclear matrix-associated CK2 which was reversed rapidly on addition of serum. Changes in the immunoreactive CK2 protein were concordant with the activity data reflecting a dynamic trafficking of the kinase in distinct phases of cell cycle. Under the same conditions, CK2 activity in total cellular lysate remained essentially unaltered. These results provide the first direct evidence of discrete modulations of CK2 in the nuclear matrix during the cell cycle progression. Inducible overexpression of CK2 in CHO cells yielded only a modest increase in CK2 activity even though a significant increase in expression was apparent at the level of CK2 alpha-specific message. Stably transfected ALVA-41 cells, however, did not show a significant change in CK2 levels despite increased expression at the message level. Not surprisingly, both types of the stably transfected cells failed to show any alteration in cell cycle progression. Distribution of the CK2 activity in the cytosolic versus nuclear matrix fractions in normal cells appears to be different from that in the cancer cells such that the ratio of nuclear matrix to cytosolic activity is much higher in the latter. Considering that nuclear matrix is central to several nuclear functions, this pattern of intracellular distribution of CK2 may have implications for its role in the oncogenic process. Published 2003 Wiley-Liss, Inc.

Protein kinase CK2 – A key suppressor of apoptosis

“…Delivery of antisense CK2α into a xenograft prostate cancer in the mouse also demonstrated potent induction of apoptosis associated with significant reduction of the CK2 signal in the nuclear matrix . Of note, analogous to results on the relation of nuclear CK2 to apoptotic signals are the observations that nuclear matrix-associated CK2 demonstrates discrete cell cycle related changes that are not apparent in the cytoplasmic compartment (Wang et al, 2003). Together, our studies indicate that a compartment of CK2 in the nucleus plays a key role in regulation of cell survival and death.…”

Emergence of protein kinase CK2 as a key target in cancer therapy

“…In the case of cell transformation, it appears that transformed cells acquire a new base level of CK2 and tend to maintain it in a stable manner analogous to that in normal cells, although in this case the cells have a dysregulated level of CK2 compared with that in the original normal cells. This accords with the lack of success in producing stable forced overexpression of CK2 protein in both normal and cancer cells [44,45]. Various observations suggest that a relatively small change in the balance of CK2 expression can have a large impact on cellular homeostasis.…”

Casein Kinase-2α1 Induces Hypertrophic Response by Phosphorylation of Histone Deacetylase 2 S394 and its Activation in the Heart

“…Previous reports have demonstrated that shuttling between the nucleus and the cytoplasm is also an important regulatory mechanism of CK2 activity in diverse biological responses. 21,22 In contrast, Hauck et al 23 recently reported that CK2␣2 does not shuttle but phosphorylates p27 in the cytoplasm in response to hypertrophic stresses in cardiomyocytes. Thus, we checked whether our CK2␣1 follows the case of CK2␣2 by observing its intracellular distribution after treatment with the hypertrophic stimulus of FBS ( Figure 4C and 4D).…”