title: Overlapping kinetochore targets of CK2 and Aurora B kinases in mitotic regulation.
abstract: Protein kinase CK2 is one of the most conserved kinases in eukaryotic cells and plays essential roles in diverse processes. While we know that CK2 plays a role(s) in cell division, our understanding of how CK2 regulates cell cycle progression is limited. In this study, we revealed a regulatory role for CK2 in kinetochore function. The kinetochore is a multi-protein complex that assembles on the centromere of a chromosome and functions to attach chromosomes to spindle microtubules. To faithfully segregate chromosomes and maintain genomic integrity, the kinetochore is tightly regulated by multiple mechanisms, including phosphorylation by Aurora B kinase. We found that a loss of CK2 kinase activity inhibits anaphase spindle elongation and results in chromosome missegregation. Moreover, a lack of CK2 activates the spindle assembly checkpoint. We demonstrate that CK2 associates with Mif2, the Saccharomyces cerevisiae homologue of human CENP-C, which serves as an important link between the inner and outer kinetochore. Furthermore, we show Mif2 and the inner kinetochore protein Ndc10 are phosphorylated by CK2, and this phosphorylation plays antagonistic and synergistic roles with Aurora B phosphorylation of these targets, respectively.
authors.affiliation: Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Yutian
authors.initials: Y
authors.lastname: Peng
authors.forename: Catherine C L
authors.initials: CC
authors.lastname: Wong
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Randall G
authors.initials: RG
authors.lastname: Tyers
authors.forename: Ali S
authors.initials: AS
authors.lastname: Sarkeshik
authors.forename: John
authors.initials: J
authors.lastname: Yates
authors.forename: David G
authors.initials: DG
authors.lastname: Drubin
authors.forename: Georjana
authors.initials: G
authors.lastname: Barnes
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D047390:Casein Kinase II / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D010957:Plasmids; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism*; D014162:Transfection
chemical_list: C081071:CBF2 protein, S cerevisiae; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C083768:MIF2 protein, S cerevisiae; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C060905:centromere protein C; D004247:DNA; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases