title: Phosphorylation of a borealin dimerization domain is required for proper chromosome segregation.
abstract: The chromosomal passenger complex (CPC) has been identified as a master regulator of mitosis. In particular, proper chromosome segregation and cytokinesis depend on the correct localization and function of the CPC. Within the complex, the kinase Aurora B associates with Incenp, Survivin, and Borealin. The stoichiometry of the complex as well as a complete understanding of how these four components interact with each other remains to be elucidated. Here, we identify a new domain of Borealin. We determined its structure using NMR spectroscopy and discovered a novel dimerization motif. Interestingly, we found that substitutions at Borealin T230, recently identified as an Mps1 phosphorylation site, can modulate the dimerization state of Borealin. Mutation of this single residue to alanine or valine impairs Aurora B activity during mitosis and causes chromosome segregation defects. This study reveals that Mps1 regulates the CPC through a novel Borealin domain.
authors.affiliation: Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco,California 94080, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Bourhis
authors.forename: Andreas
authors.initials: A
authors.lastname: Lingel
authors.forename: Qui
authors.initials: Q
authors.lastname: Phung
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Fairbrother
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Cochran
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human; D019281:Dimerization; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D053719:Tandem Mass Spectrometry
chemical_list: C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins