Inter-domain Cooperation in INCENP Promotes Aurora B Relocation from Centromeres to Microtubules
Armando van der Horst,
Martijn J.M. Vromans,
Kim Bouwman,
Maike S. van der Waal,
Michael A. Hadders,
Susanne M.A. Lens
Affiliations
Armando van der Horst
Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands
Martijn J.M. Vromans
Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands
Kim Bouwman
Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands
Maike S. van der Waal
Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands
Michael A. Hadders
Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands
Susanne M.A. Lens
Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands
The chromosomal passenger complex is essential for error-free chromosome segregation and proper execution of cytokinesis. To coordinate nuclear division with cytoplasmic division, its enzymatic subunit, Aurora B, relocalizes from centromeres in metaphase to the spindle midzone in anaphase. In budding yeast, this requires dephosphorylation of the microtubule-binding (MTB) domain of the INCENP analog Sli15. The mechanistic basis for this relocalization in metazoans is incompletely understood. We demonstrate that the putative coiled-coil domain within INCENP drives midzone localization of Aurora B via a direct, electrostatic interaction with microtubules. Furthermore, we provide evidence that the CPC multimerizes via INCENP’s centromere-targeting domain (CEN box), which increases the MTB affinity of INCENP. In (pro)metaphase, the MTB affinity of INCENP is outcompeted by the affinity of its CEN box for centromeres, while at anaphase onset—when the histone mark H2AT120 is dephosphorylated—INCENP and Aurora B switch from centromere to microtubule localization.
