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

• Published in: The Journal of cell biology 2020-03, Vol.219 (3), p.1
• Main Authors: Hadders, Michael A, Hindriksen, Sanne, Truong, My Anh, Mhaskar, Aditya N, Wopken, J Pepijn, Vromans, Martijn J M, Lens, Susanne M A
• Format: Article
• Language: English
• Subjects: Aurora B protein; Aurora Kinase B - genetics; Aurora Kinase B - metabolism; Biochemistry; Cancer; Cell Cycle and Division; Centromeres; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosome Segregation; Chromosomes; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; HCT116 Cells; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Kinesins - genetics; Kinesins - metabolism; Kinetochores - enzymology; M Phase Cell Cycle Checkpoints; Metaphase; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules - enzymology; Microtubules - genetics; Mitosis; Phosphorylation; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Signal Transduction; Substrates; Time Factors
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201907087

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.