Expression of the casein kinase 2 subunits in Chinese hamster ovary and 3T3 L1 cells provides information on the role of the enzyme in cell proliferation and the cell cycle
Dx. Li et al., Expression of the casein kinase 2 subunits in Chinese hamster ovary and 3T3 L1 cells provides information on the role of the enzyme in cell proliferation and the cell cycle, J BIOL CHEM, 274(46), 1999, pp. 32988-32996
In order to investigate the in vivo functions of protein kinase CK2 (CK2),
the expression of Myc-tagged versions of the subunits, Myc-CK2 alpha and My
c-CK2 beta, was carried out in Chinese hamster ovary cells (CHO cells) and
in 3T3 L1 fibroblasts. Cell proliferation in these cells was examined. CHO
cells that transiently overexpressed the Myc-CK2 beta subunit exhibited a s
evere growth defect, as shown by a much lower value of [H-3]thymidine incor
poration than the vector controls, and a rounded shrunken morphology. In co
ntrast, cells overexpressing Myc-tagged CK2 alpha showed a slightly but con
sistently higher value of [H-3]thymidine incorporation than the controls. T
he defect in cell growth and changes in morphology caused by Myc-CK2 beta o
verexpression were partially rescued by coexpression of Myc-tagged CK2 alph
a. In parallel to the studies in CHO cells, the stable transfection of Myc-
CK2 alpha and Myc-CK2 beta subunits was achieved in 3T3 LI fibroblast cells
. Similarly, the ectopic expression of Myc-CK2 beta, but not Myc-CK2 alpha,
caused a growth defect. By measuring [H-3]thymidine incorporation, it was
found that expression of Myc-CK2 beta prolonged the G(1) phase and inhibite
d up-regulation of cyclin DI expression during G(1). In addition, a lower m
itotic index and lower mitotic cyclin-dependent kinase activities were dete
cted in Myc-CK2 beta-expressing cells. Detailed analysis of stable cells th
at were synchronously released into the cell cycle revealed that the expres
sion of Myc-CK2 beta inhibited cells entering into mitosis and prevented th
e activation of mitotic cyclin-dependent kinases. Taken together, results f
rom both transient and stable expression of CK2 subunits strongly suggest t
hat CK2 may be involved in the control of cell growth and progression of th
e cell cycle.