title: Inhibition of aurora B kinase blocks chromosome segregation, overrides the spindle checkpoint, and perturbs microtubule dynamics in mitosis.
abstract: How kinetochores correct improper microtubule attachments and regulate the spindle checkpoint signal is unclear. In budding yeast, kinetochores harboring mutations in the mitotic kinase Ipl1 fail to bind chromosomes in a bipolar fashion. In C. elegans and Drosophila, inhibition of the Ipl1 homolog, Aurora B kinase, induces aberrant anaphase and cytokinesis. To study Aurora B kinase in vertebrates, we microinjected mitotic XTC cells with inhibitory antibody and found several related effects. After injection of the antibody, some chromosomes failed to congress to the metaphase plate, consistent with a conserved role for Aurora B in bipolar attachment of chromosomes. Injected cells exited mitosis with no evidence of anaphase or cytokinesis. Injection of anti-Xaurora B antibody also altered the microtubule network in mitotic cells with an extension of the astral microtubules and a reduction of kinetochore microtubules. Finally, inhibition of Aurora B in cultured cells and in cycling Xenopus egg extracts caused escape from the spindle checkpoint arrest induced by microtubule drugs. Our findings implicate Aurora B as a critical coordinator relating changes in microtubule dynamics in mitosis, chromosome movement in prometaphase and anaphase, signaling of the spindle checkpoint, and cytokinesis.
authors.affiliation: Department of Cell Biology, Biomedical Research Center, Room 266, 975 N.E. 10th Street, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Marko J
authors.initials: MJ
authors.lastname: Kallio
authors.forename: Mark L
authors.initials: ML
authors.lastname: McCleland
authors.forename: P Todd
authors.initials: PT
authors.lastname: Stukenberg
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Gorbsky
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D002875:Chromosomes; D008870:Microtubules / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases