Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis

• Published in: Nature communications 2011-05, Vol.2 (1), p.316-316, Article 316
• Main Authors: Saurin, Adrian T., van der Waal, Maike S., Medema, René H., Lens, Susanne M.A., Kops, Geert J.P.L.
• Format: Article
• Language: English
• Subjects: 631/45/612/1223; 631/80/641/1655; 631/80/641/1966; 631/80/86/2371; Aurora Kinase B; Aurora Kinases; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line; Cells - cytology; Cells - enzymology; Enzyme Activation; Humanities and Social Sciences; Humans; Kinetochores - enzymology; Mitosis; multidisciplinary; Protein Binding; Protein Transport; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms1319

The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis. Mitotic exit is controlled by a cell division checkpoint that prevents premature degradation of cyclin B by the anaphase-promoting complex. Saurin et al . show that Aurora B directly regulates timely establishment of this checkpoint by facilitating activation of Mps1 kinase at unattached kinetochores.