title: Feedback control in sensing chromosome biorientation by the Aurora B kinase.
abstract: Maintenance of genome stability during cell division depends on establishing correct attachments between chromosomes and spindle microtubules. Correct, bioriented attachments are stabilized, whereas incorrect attachments are selectively destabilized. This process relies largely on increased phosphorylation of kinetochore substrates of Aurora B kinase at misaligned versus aligned kinetochores. Current models explain this differential phosphorylation by spatial changes in the position of substrates relative to a constant pool of kinase at the inner centromere. However, these models are based on studies in aneuploid cells. We show that normal diploid cells have a more robust error-correction machinery. Aurora B is enriched at misaligned centromeres in these cells, and the dynamic range of Aurora B substrate phosphorylation at misaligned versus aligned kinetochores is increased. These findings indicate that in addition to Aurora B regulating kinetochore-microtubule binding, the kinetochore also controls Aurora B recruitment to the inner centromere. We show that this recruitment depends on both activity of Plk1, a kinetochore-localized kinase, and activity of Aurora B itself. Our results suggest a feedback mechanism in which Aurora B both regulates and is regulated by chromosome attachment to the spindle, which amplifies the differential phosphorylation of kinetochore substrates and increases the efficiency of error correction.
authors: Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6059, USA.
authors: Kevan J
authors: KJ
authors: Salimian
authors: Edward R
authors: ER
authors: Ballister
authors: Evan M
authors: EM
authors: Smoak
authors: Stacey
authors: S
authors: Wood
authors: Tanya
authors: T
authors: Panchenko
authors: Michael A
authors: MA
authors: Lampson
authors: Ben E
authors: BE
authors: Black
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002877:Chromosomes, Human / Q000378:metabolism*; D004171:Diploidy; D025461:Feedback, Physiological; D042822:Genomic Instability; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C576921:AURKB protein, human