title: The Ska complex promotes Aurora B activity to ensure chromosome biorientation.
abstract: Chromosome biorientation and accurate segregation rely on the plasticity of kinetochore-microtubule (KT-MT) attachments. Aurora B facilitates KT-MT dynamics by phosphorylating kinetochore proteins that are critical for KT-MT interactions. Among the substrates whose microtubule and kinetochore binding is curtailed by Aurora B is the spindle and kinetochore-associated (Ska) complex, a key factor for KT-MT stability. Here, we show that Ska is not only a substrate of Aurora B, but is also required for Aurora B activity. Ska-deficient cells fail to biorient and display chromosome segregation errors underlying suppressed KT-MT turnover. These defects coincide with KNL1-Mis12-Ndc80 network hypophosphorylation, reduced mitotic centromere-associated kinesin localization, and Aurora B T-loop phosphorylation at kinetochores. We further show that Ska requires its microtubule-binding capability to promote Aurora B activity in cells and stimulates Aurora B catalytic activity in vitro. Finally, we show that protein phosphatase 1 counteracts Aurora B activity to enable Ska kinetochore accumulation once biorientation is achieved. We propose that Ska promotes Aurora B activity to limit its own microtubule and kinetochore association and to ensure that KT-MT dynamics and stability fall within an optimal balance for biorientation.
authors.affiliation: Growth and Development, Biozentrum, University of Basel, 4056 Basel, Switzerland.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Redli
authors.affiliation: Department of Cell Physiology and Metabolism, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Ivana
authors.identifier: http://orcid.org/0000-0002-4824-8174
authors.initials: I
authors.lastname: Gasic
authors.affiliation: Department of Cell Physiology and Metabolism, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Patrick
authors.identifier: http://orcid.org/0000-0001-9742-8756
authors.initials: P
authors.lastname: Meraldi
authors.affiliation: Growth and Development, Biozentrum, University of Basel, 4056 Basel, Switzerland.
authors.forename: Erich A
authors.identifier: http://orcid.org/0000-0003-4835-5719
authors.initials: EA
authors.lastname: Nigg
authors.affiliation: Growth and Development, Biozentrum, University of Basel, 4056 Basel, Switzerland Cell Cycle and Cancer, Group of Biomedical Research in Gynecology, Vall d'Hebron Research Institute (VHIR)-UAB, 08035 Barcelona, Spain anna.santamaria@vhir.org.
authors.forename: Anna
authors.identifier: http://orcid.org/0000-0001-6726-8990
authors.initials: A
authors.lastname: Santamaria
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism*; D055162:Biocatalysis; D002503:Centromere / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D045584:Chromosome Positioning; D020090:Chromosome Segregation; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D046912:Multiprotein Complexes; D064107:Aurora Kinase B; D054645:Protein Phosphatase 1