Inducible expression of the regulatory protein kinase CK2beta subunit: incorporation into complexes with catalytic CK2 subunits and re-examination of the effects of CK2beta on cell proliferation.
The regulatory subunit of protein kinase CK2, designated CK2beta, exists both free in cells and in complexes with the CK2 catalytic subunits. Growing evidence suggests that CK2beta has functions dependent and independent of the CK2 catalytic subunits. There have been indications that CK2beta has functions associated with DNA damage responses and in the control of cell proliferation. For example, transient and stable constitutive overexpression of CK2beta 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 CK2beta on cell proliferation, we generated human osteosarcoma U2OS cell lines with tetracycline-regulated expression of CK2beta. Increased expression of CK2beta 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 CK2beta in cells. Mouse 3T3-L1 cells stably transfected with CK2beta also showed no alterations in cell proliferation. The differences between these results and those previously reported emphasize the complex nature of CK2beta and its cellular functions. Furthermore, these results indicate that increased expression of CK2beta is not by itself sufficient to effect alterations in cell proliferation.
Vilk
G
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Department of Biochemistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1.
Derksen
D R
DR
Litchfield
D W
DW
D016475:3T3 Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D047390:Casein Kinase II; D020134:Catalytic Domain / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004249:DNA Damage / Q000502:physiology / Q000528:radiation effects; D004790:Enzyme Induction; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D012516:Osteosarcoma / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000378:metabolism; D021122:Protein Subunits; D013752:Tetracycline / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D046911:Macromolecular Substances; D021122:Protein Subunits; D016159:Tumor Suppressor Protein p53; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D013752:Tetracycline