title: Spindle checkpoint silencing: PP1 tips the balance.
abstract: The spindle checkpoint is a mitotic surveillance mechanism that delays anaphase until all sister chromatids are correctly attached to microtubules from opposite poles. Recent studies reveal that protein kinase Aurora B is a key regulator of spindle checkpoint activation whereas protein phosphatase PP1 antagonizes Aurora B and induces checkpoint silencing. Chromosome biorientation stretches the kinetochores and spatially separates centromeric Aurora B from its kinetochore substrates, comprising several PP1-interacting proteins (PIPs). The ensuing dephosphorylation of these PIPs creates docking sites for the bulk recruitment of PP1 to the kinetochores. We propose that this tension-induced targeting of PP1 triggers checkpoint silencing by the dephosphorylation of kinetochore and checkpoint components, including Aurora B substrates. In addition, PP1 also directly inactivates a kinetochore-associated pool of Aurora B and silences checkpoint signaling by opposing the centromeric targeting of Aurora B.
authors.affiliation: Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Lesage
authors.forename: Junbin
authors.initials: J
authors.lastname: Qian
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bollen
mesh_terms: D000705:Anaphase; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D059447:Cell Cycle Checkpoints; D002842:Chromatids / Q000378:metabolism; D020090:Chromosome Segregation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D015003:Yeasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D054645:Protein Phosphatase 1