Chromatin protein HP1 interacts with the mitotic regulator borealin protein and specifies the centromere localization of the chromosomal passenger complex

J Biol Chem. 2014 Jul 25;289(30):20638-49. doi: 10.1074/jbc.M114.572842.

Abstract

Accurate mitosis requires the chromosomal passenger protein complex (CPC) containing Aurora B kinase, borealin, INCENP, and survivin, which orchestrates chromosome dynamics. However, the chromatin factors that specify the CPC to the centromere remain elusive. Here we show that borealin interacts directly with heterochromatin protein 1 (HP1) and that this interaction is mediated by an evolutionarily conserved PXVXL motif in the C-terminal borealin with the chromo shadow domain of HP1. This borealin-HP1 interaction recruits the CPC to the centromere and governs an activation of Aurora B kinase judged by phosphorylation of Ser-7 in CENP-A, a substrate of Aurora B. Consistently, modulation of the motif PXVXL leads to defects in CPC centromere targeting and aberrant Aurora B activity. On the other hand, the localization of the CPC in the midzone is independent of the borealin-HP1 interaction, demonstrating the spatial requirement of HP1 in CPC localization to the centromere. These findings reveal a previously unrecognized but direct link between HP1 and CPC localization in the centromere and illustrate the critical role of borealin-HP1 interaction in orchestrating an accurate cell division.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Division / physiology*
  • Centromere / genetics
  • Centromere / metabolism*
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes, Human / genetics
  • Chromosomes, Human / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Protein Structure, Tertiary

Substances

  • CDCA8 protein, human
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Chromobox Protein Homolog 5
  • AURKB protein, human
  • Aurora Kinase B