Inducible expression of the regulatory protein kinase CK2β subunit:: Incorporation into complexes with catalytic CK2 subunits and re-examination of the effects of CK2β on cell proliferation

The regulatory subunit of protein kinase CK2, designated CK2 beta, exists both free in cells and in complexes with the CK2 catalytic subunits. Growing evidence suggests that CK2 beta has functions dependent and independent of the CK2 catalytic subunits. There have been indications that CK2 beta has functions associated with DNA damage responses and in the control of cell proliferation. For example, transient and stable constitutive overexpression of CK2 beta in mammalian cells was previously shown to perturb cell cycle progression and to attenuate proliferation. To systematically investigate the molecular mechanisms responsible for these effects of CK2P an cell proliferation, we generated human osteosarcoma U2OS cell lines with tetracycline-regulated expression of CK2P. Increased expression of CK2P results in increases in total cellular CK2 activity, but no changes in cell cycle profiles or proliferation. Furthermore, following exposure to ultraviolet radiation, p53 induction was identical regardless of the levels of CK2P in cells. Mouse 3T3-L1 cells stably transfected with CK2P also showed no alterations in cell proliferation. The differences between these results and those previously reported emphasize the complex nature of CK2 beta and its cellular functions. Furthermore, these results indicate that increased expression of CK2P is not by itself sufficient to effect alterations in cell proliferation. (C) 2001 Wiley-Liss, Inc.