Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis

Michael A. Hadders, Sanne Hindriksen, My Anh Truong, Aditya N. Mhaskar, J. Pepijn Wopken, Martijn J.M. Vromans, Susanne M.A. Lens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
4 Downloads (Pure)

Abstract

Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase-dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT-MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of the current spatial models for how tension affects Aurora B-dependent kinetochore phosphorylation.

Original languageEnglish
Article numbere201907087
Number of pages27
JournalJournal of Cell Biology
Volume219
Issue number3
DOIs
Publication statusPublished - 2 Mar 2020

Keywords

  • Aurora Kinase B/genetics
  • Chromosomal Proteins, Non-Histone/genetics
  • Chromosome Segregation
  • Cytoskeletal Proteins/genetics
  • HCT116 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins/genetics
  • Kinesin/genetics
  • Kinetochores/enzymology
  • M Phase Cell Cycle Checkpoints
  • Microtubule-Associated Proteins/genetics
  • Microtubules/enzymology
  • Mitosis
  • Phosphorylation
  • Protein-Serine-Threonine Kinases/genetics
  • Signal Transduction
  • Time Factors

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