title: Multiple Levels of Regulation of Sororin by Cdk1 and Aurora B.
abstract: The cohesin complex holds sister chromatids together until all chromosomes are properly attached to the mitotic spindle. Cleavage of the cohesin subunit Rad21 at the metaphase to anaphase transition allows separation of sister chromatids and is fundamental for the creation of identical daughter cells. Sororin blocks removal of cohesin from chromosomes from S phase until mitosis. In mitosis, Sororin is phosphorylated by Cdk1 releasing it from the cohesin complex. Aurora B phosphorylation of Sororin may play a similar role as Cdk1. Using PhosTag electrophoresis, we detect multiple Sororin species suggesting that phosphorylation of Sororin in mitosis is heterogeneous. Mutating the Cdk1 consensus site S21 to alanine eliminates many of the phosphorylated species suggesting that S21 is a key site of phosphorylation in vivo. Inhibiting Aurora B reduces phosphorylation of Sororin in cells, but only if Cdk1 sites are intact suggesting that some phosphorylation events on Sororin may be sequential. Surprisingly, mutating Aurora B consensus sites in Sororin causes it to relocalize to the nucleolus during interphase and blocks its interaction with chromosomes in Aurora B-inhibited cells. These observations indicate that phosphorylation plays unexpected roles in regulating the subcellular localization of Sororin.
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio, 43606.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Borton
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio, 43606.
authors.forename: Maisha S
authors.initials: MS
authors.lastname: Rashid
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio, 43606.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Dreier
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, Ohio, 43606.
authors.forename: William R
authors.initials: WR
authors.lastname: Taylor
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D064107:Aurora Kinase B / Q000502:physiology*; D001665:Binding Sites; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism; D016384:Consensus Sequence; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D013379:Substrate Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C500695:CDCA5 protein, human; D018797:Cell Cycle Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: COHESIN; MITOSIS; NUCLEOLUS; PHOSPHORYLATION; PHOSTAG