title: Aurora B and Cdk1 mediate Wapl activation and release of acetylated cohesin from chromosomes by phosphorylating Sororin.
abstract: Sister chromatid cohesion depends on Sororin, a protein that stabilizes acetylated cohesin complexes on DNA by antagonizing the cohesin release factor Wings-apart like protein (Wapl). Cohesion is essential for chromosome biorientation but has to be dissolved to enable sister chromatid separation. To achieve this, the majority of cohesin is removed from chromosome arms in prophase and prometaphase in a manner that depends on Wapl and phosphorylation of cohesin's subunit stromal antigen 2 (SA2), whereas centromeric cohesin is cleaved in metaphase by the protease separase. Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion. At centromeres, the cohesin protector shugoshin (Sgo1)-protein phosphatase 2A (PP2A) antagonizes Aurora B and Cdk1 partly by dephosphorylating Sororin and thus maintains cohesion until metaphase. We propose that the stepwise loss of cohesion between chromosome arms and centromeres is caused by local regulation of Wapl activity, which is controlled by the phosphorylation state of Sororin.
authors.affiliation: Research Institute of Molecular Pathology, A-1030 Vienna, Austria. nishiyama@bio.nagoya-u.ac.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Martina M
authors.initials: MM
authors.lastname: Sykora
authors.forename: Pim J
authors.initials: PJ
authors.lastname: Huis in 't Veld
authors.forename: Karl
authors.initials: K
authors.lastname: Mechtler
authors.forename: Jan-Michael
authors.initials: JM
authors.lastname: Peters
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000494:pharmacology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D002875:Chromosomes / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014981:Xenopus; D000097722:Cohesins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097722:Cohesins; C500695:CDCA5 protein, human; C488092:WAPL protein, human; C576921:AURKB protein, human
keywords: cell cycle; chromosome segregation; prophase pathway
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