title: A mathematical model of Aurora B activity in prophase and metaphase.
abstract: Aurora B kinase is a protein that controls several processes in mitosis when it is found associated with INCENP, Survivin and Borealin in a complex known as the Chromosomal Passenger Complex. Aurora B in complex with INCENP is phosphorylated on three sites, resulting in the full activation of Aurora B. In prophase and metaphase, Aurora B is activated at centromeres, the region of chromatin linking sister chromatids, due to an autophosphorylation mechanism, and it has been hypothesised that Aurora B is activated throughout the cytoplasm due to its concentration at centromeres. In this article, we first develop a time-dependent model of Aurora B activation that does not incorporate spatial variation. This model is used to demonstrate the various qualitative behaviours that the activation of Aurora B is capable of displaying for different model parameters. Next, we develop a spatio-temporal model of Aurora B activation that includes diffusion of soluble Aurora B and binding of Aurora B to immobile centromeric binding sites. This model describes the activation of Aurora B throughout the cytoplasm due to its concentration-dependent activation at centromeres. The models demonstrate the effects that a soluble phosphatase concentration, multisite phosphorylation and diffusion have on the activation of Aurora B.
authors.affiliation: School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, University Road, Galway, Ireland; AgroParisTech, CRNH-IdF, UMR914, Nutrition Physiology and Ingestive Behavior, Paris F-75005, France; INRA, CRNH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, Paris F-75005, France. Electronic address: kevin.doherty@agroparistech.fr.
authors.forename: Kevin
authors.initials: K
authors.lastname: Doherty
authors.affiliation: School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, University Road, Galway, Ireland. Electronic address: martin.meere@nuigalway.ie.
authors.forename: Martin
authors.initials: M
authors.lastname: Meere
authors.affiliation: School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, University Road, Galway, Ireland. Electronic address: petri.piiroinen@nuigalway.ie.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Piiroinen
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism*; D002503:Centromere; D008962:Models, Theoretical
chemical_list: D064107:Aurora Kinase B
keywords: Aurora B; Binding; Centromere; Diffusion; Mathematical modelling