title: Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation.
abstract: The chromosome passenger complex (CPC) controls chromosome congression, kinetochore-microtubule attachments, and spindle checkpoint signaling during mitosis. Aurora-B kinase is the catalytic subunit of the CPC. To understand how a single kinase can regulate such diverse events, we have investigated the activation of Aurora-B and describe two distinct activation mechanisms. First, Aurora-B activation in vitro requires two cofactors, telophase disc-60kD (TD-60) and microtubules. TD-60 is critical to localize both the CPC and Haspin kinase activity to centromeres and thus regulates Aurora-B at several levels. Second, Aurora-B substrates can inhibit kinase activation, and this is relieved by phosphorylation of these substrates by the centromeric kinases Plk1 and Haspin. These regulatory mechanisms suggest models for phosphorylation by Aurora-B of centromeric substrates at unaligned chromosomes and merotelic attachments.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Rosasco-Nitcher
authors.forename: Weijie
authors.initials: W
authors.lastname: Lan
authors.forename: Sepideh
authors.initials: S
authors.lastname: Khorasanizadeh
authors.forename: P Todd
authors.initials: PT
authors.lastname: Stukenberg
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D029867:Xenopus Proteins; C506222:INCENP protein, Xenopus; C526314:RCC2 protein, Xenopus; C509242:mitotic centromere-associated kinesin, Xenopus; C101085:Plk1 protein, Xenopus; D000097869:Polo-Like Kinase 1