title: Regulation of caspase pathways by protein kinase CK2: identification of proteins with overlapping CK2 and caspase consensus motifs.
abstract: Apoptosis, or programmed cell death, is a vital cellular process often impaired in diseases such as cancer. Aspartic acid-directed proteases known as caspases cleave a broad spectrum of cellular proteins and are central constituents of the apoptotic machinery. Caspases are regulated by a variety of mechanisms including protein phosphorylation. One intriguing mechanism by which protein kinases can modulate caspase pathways is by blocking substrate cleavage through phosphorylation of residues adjacent to caspase cleavage sites. To explore this mechanism in detail, we recently undertook a systematic investigation using a combination of bioinformatics, peptide arrays, and peptide cleavage assays to identify proteins with overlapping protein kinase and caspase recognition motifs (Duncan et al., Sci Signal 4:ra30, 2011). These studies implicated protein kinase CK2 as a global regulator of apoptotic pathways. In this article, we extend the analysis of proteins with overlapping CK2 and caspase consensus motifs to examine the convergence of CK2 with specific caspases and to identify CK2/caspase substrates known to be phosphorylated or cleaved in cells. Given its constitutive activity and elevated expression in cancer, these observations suggest that the ability of CK2 to modulate caspase pathways may contribute to a role in promoting cancer cell survival and raise interesting prospects for therapeutic targeting of CK2.
authors.affiliation: Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Turowec
authors.forename: James S
authors.initials: JS
authors.lastname: Duncan
authors.forename: Greg B
authors.initials: GB
authors.lastname: Gloor
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D047390:Casein Kinase II / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D016384:Consensus Sequence; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D010455:Peptides; D047390:Casein Kinase II; D020169:Caspases