title: Characterizing the convergence of protein kinase CK2 and caspase-3 reveals isoform-specific phosphorylation of caspase-3 by CK2α': implications for pathological roles of CK2 in promoting cancer cell survival.
abstract: Protein kinase CK2 has emerged as a promising candidate for the treatment of a number of cancers. This enzyme is comprised of two catalytic subunits (CK2 and/or CK2α') that form complexes with homodimers of regulatory CK2β subunits. While catalytic and regulatory CK2 subunits are generally expressed at similar levels to form tetrameric complexes, asymmetric expression of CK2 subunits has been associated with various forms of cancer and the enhanced survival of cancer cells. To elucidate mechanisms responsible for regulation of cancer cell survival by CK2, we recently employed computational and experimental strategies that revealed widespread overlap between sites for CK2 phosphorylation and caspase cleavage. Among candidates with overlapping CK2 and caspase cleavage sites was caspase-3 that is phosphorylated by CK2 to prevent its activation by upstream caspases. To elucidate the precise relationship between CK2 and caspase-3, we modulated expression of individual CK2 subunits and demonstrated that CK2α' exhibits a striking preference for caspase-3 phosphorylation in cells as compared to CK2α and that CK2β exhibits the capacity to abolish caspase-3 phosphorylation. Since caspase-3 represents the first CK2 substrate selectively phosphorylated by CK2α' in cells, our work highlights divergent functions of the different forms of CK2. Given the involvement of CK2 in a diverse series of biological events and its association with various cancers, this work has important implications for identifying pathological roles of distinct forms of CK2 that could instruct efforts to selectively target individual CK2 subunits for therapy.
authors.affiliation: Department of Biochemistry, Schulich School of Medicine, Western University, London, ON, Canada.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Turowec
authors.forename: Greg
authors.initials: G
authors.lastname: Vilk
authors.forename: Michelle
authors.initials: M
authors.lastname: Gabriel
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D047390:Casein Kinase II / Q000737:chemistry* / Q000378:metabolism*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D002470:Cell Survival; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D007527:Isoenzymes; D047390:Casein Kinase II; C505407:CASP3 protein, human; D053148:Caspase 3