title: Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction.
abstract: Fidelity of chromosome segregation is ensured by a tension-dependent error correction system that prevents stabilization of incorrect chromosome-microtubule attachments. Unattached or incorrectly attached chromosomes also activate the spindle assembly checkpoint, thus delaying mitotic exit until all chromosomes are bioriented. The Aurora B kinase is widely recognized as a component of error correction. Conversely, its role in the checkpoint is controversial. Here, we report an analysis of the role of Aurora B in the spindle checkpoint under conditions believed to uncouple the effects of Aurora B inhibition on the checkpoint from those on error correction. Partial inhibition of several checkpoint and kinetochore components, including Mps1 and Ndc80, strongly synergizes with inhibition of Aurora B activity and dramatically affects the ability of cells to arrest in mitosis in the presence of spindle poisons. Thus, Aurora B might contribute to spindle checkpoint signalling independently of error correction. Our results support a model in which Aurora B is at the apex of a signalling pyramid whose sensory apparatus promotes the concomitant activation of error correction and checkpoint signalling pathways.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Santaguida
authors.forename: Claudio
authors.initials: C
authors.lastname: Vernieri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Villa
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciliberto
authors.forename: Andrea
authors.initials: A
authors.lastname: Musacchio
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D020090:Chromosome Segregation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D008941:Spindle Apparatus / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases