Targeting the INCENP in-box-Aurora B interaction to inhibit CPC activity in vivo

Florence H. Gohard, Daniel J. St-Cyr, Mike Tyers, William C. Earnshaw*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The chromosome passenger complex (CPC) is an essential regulator of mitosis and cytokinesis. The CPC consists of Aurora B kinase, inner centromere protein (INCENP), and the targeting subunits survivin and borealin/Dasra B. INCENP is a scaffolding subunit for the CPC and activates Aurora B via its conserved IN-box domain. We show that overexpression of soluble IN-box in HeLa cells affects endogenous CPC localization and produces a significant increase in multinucleated and micronucleated cells consistent with CPC loss of function. The dominant-negative effect of soluble IN-box expression depends on residues corresponding to hINCENP W845 and/or F881, suggesting that these are essential for Aurora B binding in vivo. We then screened a targeted library of small (five to nine residues long) circular peptide (CP) IN-box fragments generated using split intein circular ligation of proteins and peptides (SICLOPPS) methodology. We identified a number of CPs that caused modest but reproducible increases in rates of multinucleated and micronucleated cells. Our results provide proof of concept that inhibition of the Aurora B-IN-box interaction is a viable strategy for interfering with CPC function in vivo. & 2014 The Authors. Published.

Original languageEnglish
Article number140163
JournalOpen Biology
Volume4
Issue number11
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Aurora B
  • Chromosomal passenger complex
  • Cyclic peptide
  • Cytokinesis
  • INCENP
  • Mitosis

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