title: Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment.
abstract: Maintenance of chromosomal stability relies on coordination between various processes that are critical for proper chromosome segregation in mitosis. Here we show that monopolar spindle 1 (Mps1) kinase, which is essential for the mitotic checkpoint, also controls correction of improper chromosome attachments. We report that Borealin/DasraB, a member of the complex that regulates the Aurora B kinase, is directly phosphorylated by Mps1 on residues that are crucial for Aurora B activity and chromosome alignment. As a result, cells lacking Mps1 kinase activity fail to efficiently align chromosomes due to impaired Aurora B function at centromeres, leaving improper attachments uncorrected. Strikingly, Borealin/DasraB bearing phosphomimetic mutations restores Aurora B activity and alignment in Mps1-depleted cells. Mps1 thus coordinates attachment error correction and checkpoint signaling, two crucial responses to unproductive chromosome attachments.
authors.affiliation: Department of Medical Oncology, Laboratory of Experimental Oncology, UMC Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
authors.forename: Nannette
authors.initials: N
authors.lastname: Jelluma
authors.forename: Arjan B
authors.initials: AB
authors.lastname: Brenkman
authors.forename: Niels J F
authors.initials: NJ
authors.lastname: van den Broek
authors.forename: Carin W A
authors.initials: CW
authors.lastname: Cruijsen
authors.forename: Maria H J
authors.initials: MH
authors.lastname: van Osch
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: Lens
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
authors.forename: Geert J P L
authors.initials: GJ
authors.lastname: Kops
mesh_terms: D000483:Alleles; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D014162:Transfection
chemical_list: C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human