In order to investigate the in vivo functions of protein kinase CK2 (CK2), the expression of Myc-tagged versions of the subunits, Myc-CK2␣ and Myc-CK2, was carried out in Chinese hamster ovary cells (CHO cells) and in 3T3 L1 fibroblasts. Cell proliferation in these cells was examined. CHO 3 H]thymidine incorporation, it was found that expression of Myc-CK2 prolonged the G 1 phase and inhibited up-regulation of cyclin D1 expression during G 1 . In addition, a lower mitotic index and lower mitotic cyclin-dependent kinase activities were detected in Myc-CK2-expressing cells. Detailed analysis of stable cells that were synchronously released into the cell cycle revealed that the expression of Myc-CK2 inhibited cells entering into mitosis and prevented the activation of mitotic cyclin-dependent kinases. Taken together, results from both transient and stable expression of CK2 subunits strongly suggest that CK2 may be involved in the control of cell growth and progression of the cell cycle.
Casein kinase 2 (CK2)1 is a ubiquitous, multifunctional eukaryotic serine/threonine protein kinase that phosphorylates many different substrates including metabolic enzymes, structural proteins, transcription factors, and proto-oncoproteins (1). The holoenzyme form of CK2 is a heterotetramer, composed of ␣, ␣Ј, and  subunits combined to form ␣ 2  2 , ␣␣Ј 2 , and ␣Ј 2  2 . The ␣ and ␣Ј subunits are catalytically active, whereas the  subunit is thought to be a regulatory subunit that stimulates the catalytic activity of ␣ or ␣Ј subunits and may also influence substrate specificity (for reviews, see Refs. 1-4). CK2 exhibits remarkable evolutionary conservation of primary structure in all eukaryotes from yeast to human, e.g. the identity of amino acid sequences of ␣ and  subunits between human and Drosophila melanogaster is 90 and 88%, respectively. The amino acid sequences of the  subunits of human, pig, and chicken are even identical, underscoring this point (5-6).The physiological role of CK2 has been explored in yeast and in a number of mammalian cell types, and these studies suggest that the enzyme is involved in cell growth and progression of the cell cycle. For example, genetic studies in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Dictyostelium discoideum (7-9) showed that CK2 activity is essential for cell viability, e.g. the simultaneous disruption of the genes encoding the catalytic subunits, cka1 and cka2, in S. cerevisiae is lethal (7). An essential role of CK2 in control of cell cycle progression has also been demonstrated in the yeast S. cerevisiae (10). Through the use of mutant strains temperaturesensitive for the CK2 gene, the function of CK2 during the cell cycle was analyzed. It was shown that following a shift to the nonpermissive temperature, the mutant strains arrested within a single cell cycle and showed a dual arrest phenotype consisting of 50% of cells in G 1 and 50% cells in G 2 /M. Further analysis by flow cytometry of pheromone-synchronized cells confirmed that CK2 is required at a...