title: Inter-domain Cooperation in INCENP Promotes Aurora B Relocation from Centromeres to Microtubules.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands.
authors.forename: Armando
authors.initials: A
authors.lastname: van der Horst
authors.affiliation: Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands.
authors.forename: Martijn J M
authors.initials: MJ
authors.lastname: Vromans
authors.affiliation: Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Bouwman
authors.affiliation: Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands.
authors.forename: Maike S
authors.initials: MS
authors.lastname: van der Waal
authors.affiliation: Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hadders
authors.affiliation: Department of Medical Oncology, Department of Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, the Netherlands. Electronic address: s.m.a.lens@umcutrecht.nl.
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: Lens
mesh_terms: D000705:Anaphase; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation; D006367:HeLa Cells / Q000502:physiology; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D064107:Aurora Kinase B