Inter-domain Cooperation in INCENP Promotes Aurora B Relocation from Centromeres to Microtubules

Cell Rep. 2015 Jul 21;12(3):380-7. doi: 10.1016/j.celrep.2015.06.038. Epub 2015 Jul 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism*
  • Centromere / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation
  • HeLa Cells / physiology
  • Humans
  • Microtubules / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary

Substances

  • Chromosomal Proteins, Non-Histone
  • Aurora Kinase B