A mathematical model of Aurora B activity in prophase and metaphase

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.