title: Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres.
abstract: Shugoshin (Sgo) is a conserved centromeric protein. Mammalian Sgo1 collaborates with protein phosphatase 2A (PP2A) to protect mitotic cohesin from the prophase dissociation pathway. Although another shugoshin-like protein, Sgo2, is required for the centromeric protection of cohesion in germ cells, its precise molecular function remains largely elusive. We demonstrate that hSgo2 plays a dual role in chromosome congression and centromeric protection of cohesion in HeLa cells, while the latter function is exposed only in perturbed mitosis. These functions partly overlap with those of Aurora B, a kinase setting faithful chromosome segregation. Accordingly, we identified the phosphorylation of hSgo2 by Aurora B at the N-terminal coiled-coil region and the middle region, and showed that these phosphorylations separately promote binding of hSgo2 to PP2A and MCAK, factors required for centromeric protection and chromosome congression, respectively. Furthermore, these phosphorylations are essential for localizing PP2A and MCAK to centromeres. This mechanism seems applicable to germ cells as well. Thus, our study identifies Sgo2 as a hitherto unknown crucial cellular substrate of Aurora B in mammalian cells.
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanno
authors.forename: Tomoya S
authors.initials: TS
authors.lastname: Kitajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Ando
authors.forename: Kei-Ichiro
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002503:Centromere / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D018797:Cell Cycle Proteins; C091489:KIF2C protein, human; C510590:SGO2 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2; D016547:Kinesins