title: Functional interplay between Aurora B kinase and Ssu72 phosphatase regulates sister chromatid cohesion.
abstract: Cohesins establish cohesion between replicated sister chromatids and are maintained as a multiprotein complex on chromosome arms until they are phosphorylated by mitotic kinases, such as Aurora B and Plk1. However, the mechanics of how the phosphorylation and dephosphorylation of cohesin subunits by kinases and phosphatases, respectively, leads to the dissociation of the cohesin complex from chromosomes remain unclear. Here we report that Aurora B kinase directly interacts with and phosphorylates Ssu72, a new cohesin-binding phosphatase, at Ser 19 in vitro and in vivo. The Aurora B-mediated phosphorylation of Ssu72 causes the structural modification of Ssu72 protein, downregulates phosphatase activity and triggers the ubiquitin-dependent degradation of Ssu72. Overexpression of the Aurora B-mediated phosphomimetic mutant of Ssu72 prevents maintainance chromosome arm cohesion. These results provide evidence that Aurora B kinase directly targets Ssu72 phosphatase for regulation of sister chromatid cohesion during early mitosis.
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Se-Hyuk
authors.initials: SH
authors.lastname: Kim
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Janet
authors.initials: J
authors.lastname: Lee
authors.forename: Jong Hyuk
authors.initials: JH
authors.lastname: Yoon
authors.forename: Sunkyu
authors.initials: S
authors.lastname: Choi
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Cho
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D064107:Aurora Kinase B / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002842:Chromatids; D020090:Chromosome Segregation; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D012854:Sister Chromatid Exchange
chemical_list: D002352:Carrier Proteins; D012694:Serine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D010749:Phosphoprotein Phosphatases; C496300:SSU72 protein, human