title: Phosphorylation of PP1 Regulator Sds22 by PLK1 Ensures Accurate Chromosome Segregation.
abstract: During cell division, accurate chromosome segregation is tightly regulated by Polo-like kinase 1 (PLK1) and opposing activities of Aurora B kinase and protein phosphatase 1 (PP1). However, the regulatory mechanisms underlying the aforementioned hierarchical signaling cascade during mitotic chromosome segregation have remained elusive. Sds22 is a conserved regulator of PP1 activity, but how it regulates PP1 activity in space and time during mitosis remains elusive. Here we show that Sds22 is a novel and cognate substrate of PLK1 in mitosis, and the phosphorylation of Sds22 by PLK1 elicited an inhibition of PP1-mediated dephosphorylation of Aurora B at threonine 232 (Thr232) in a dose-dependent manner. Overexpression of a phosphomimetic mutant of Sds22 causes a dramatic increase in mitotic delay, whereas overexpression of a non-phosphorylatable mutant of Sds22 results in mitotic arrest. Mechanistically, the phosphorylation of Sds22 by PLK1 strengthens the binding of Sds22 to PP1 and inhibits the dephosphorylation of Thr232of Aurora B to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling hierarchy that orchestrates dynamic protein phosphorylation and dephosphorylation of critical mitotic regulators during chromosome segregation to guard chromosome stability.
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China, the Morehouse School of Medicine and Atlanta Clinical & Translational Science Institute, Atlanta, Georgia 30310.
authors.forename: Hequan
authors.initials: H
authors.lastname: Duan
authors.affiliation: the National Chromatographic Research and Analysis Center, Chinesse Academy of Sciences, Dalian 116023, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Wang
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China.
authors.forename: Xinjiao
authors.initials: X
authors.lastname: Gao
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China.
authors.forename: Maomao
authors.initials: M
authors.lastname: Yan
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China.
authors.forename: Saima
authors.initials: S
authors.lastname: Akram
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: the National Chromatographic Research and Analysis Center, Chinesse Academy of Sciences, Dalian 116023, China.
authors.forename: Hanfa
authors.initials: H
authors.lastname: Zou
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China, the Morehouse School of Medicine and Atlanta Clinical & Translational Science Institute, Atlanta, Georgia 30310.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Chu
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
authors.affiliation: the Morehouse School of Medicine and Atlanta Clinical & Translational Science Institute, Atlanta, Georgia 30310.
authors.forename: Gregory
authors.initials: G
authors.lastname: Barrett
authors.affiliation: the Morehouse School of Medicine and Atlanta Clinical & Translational Science Institute, Atlanta, Georgia 30310.
authors.forename: Hadiyah-Nicole
authors.initials: HN
authors.lastname: Green
authors.affiliation: the National Chromatographic Research and Analysis Center, Chinesse Academy of Sciences, Dalian 116023, China.
authors.forename: Fangjun
authors.initials: F
authors.lastname: Wang
authors.affiliation: the Guangzhou Women and Children's Medical Center, Guangzhou 510623, China, and the Center of Molecular Proteomics, South University of Science & Technology of China, Shenzhen 518055, China.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Tian
authors.affiliation: the Guangzhou Women and Children's Medical Center, Guangzhou 510623, China, and the Center of Molecular Proteomics, South University of Science & Technology of China, Shenzhen 518055, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China, the Morehouse School of Medicine and Atlanta Clinical & Translational Science Institute, Atlanta, Georgia 30310, wwwang@mail.ustc.edu.cn.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China, the Morehouse School of Medicine and Atlanta Clinical & Translational Science Institute, Atlanta, Georgia 30310, xing1017@ustc.edu.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: From the Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, MOE Collaborative Innovation Center of Chemistry for Life Sciences, University of Science & Technology of China, Hefei 230027, China, yaoxb@ustc.edu.cn.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D000705:Anaphase / Q000502:physiology*; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D043171:Chromosomal Instability / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase / Q000502:physiology*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D064107:Aurora Kinase B; D018797:Cell Cycle Proteins; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C509751:PPP1R7 protein, human; C576921:AURKB protein, human
keywords: cell cycle; centromere; cyclin-dependent kinase (CDK); cytoskeleton; kinetochore; phosphatase; phosphorylation; tubulin