title: Phosphorylation regulates the stability of the regulatory CK2beta subunit.
abstract: Protein kinase CK2 is a protein serine/threonine kinase that exhibits elevated expression in a number of cancers and displays oncogenic activity in mice. The regulatory CK2beta subunit has a central role in assembly of functional tetrameric CK2 complexes where it participates in modulation of catalytic activity and substrate specificity. Since overexpression of CK2beta results in elevated levels of CK2 activity, we investigated the molecular mechanisms that control its degradation since perturbations in these pathways could contribute to elevated CK2 in cancer. In this study, we demonstrate that CK2beta is degraded by a proteasome-dependent pathway and that it is ubiquitinated. We have also investigated the role of phosphorylation and a putative destruction box in regulating its stability in cells. Importantly, replacement of three serine residues within the autophosphorylation site of CK2beta with glutamic acid residues resulted in a significant decrease in its degradation indicating that autophosphorylation is involved in regulating its stability. Notably, although the autophosphorylation site of CK2beta is remarkably conserved between species, this is the first functional role ascribed to this site. Furthermore, based on these results, we speculate that alterations in the phosphorylation or dephosphorylation of the regulatory CK2beta subunit could underlie the elevated expression of CK2 that is observed in cancer cells.
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Cunjie
authors.initials: C
authors.lastname: Zhang
authors.forename: Greg
authors.initials: G
authors.lastname: Vilk
authors.forename: David A
authors.initials: DA
authors.lastname: Canton
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
mesh_terms: D000818:Animals; D019556:COS Cells; D047390:Casein Kinase II; D002645:Chickens; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004795:Enzyme Stability / Q000187:drug effects; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D021122:Protein Subunits; D014452:Ubiquitins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex