title: Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis.
abstract: 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.
authors.affiliation: Molecular Cancer Research and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands.
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Saurin
authors.forename: Maike S
authors.initials: MS
authors.lastname: van der Waal
authors.forename: René H
authors.initials: RH
authors.lastname: Medema
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: Lens
authors.forename: Geert J P L
authors.initials: GJ
authors.lastname: Kops
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002477:Cells / Q000166:cytology* / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D018386:Kinetochores / Q000201:enzymology; D008938:Mitosis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases
chemical_list: D018797:Cell Cycle Proteins; D011505:Protein-Tyrosine Kinases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human