title: Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation.
abstract: Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase-promoting complex/cyclosome-inhibitory complexes to levels that ensure long-term SAC activity. We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function.
authors.affiliation: Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. cconde@ibmc.up.pt
authors.forename: Carlos
authors.initials: C
authors.lastname: Conde
authors.forename: Mariana
authors.initials: M
authors.lastname: Osswald
authors.forename: João
authors.initials: J
authors.lastname: Barbosa
authors.forename: Tatiana
authors.initials: T
authors.lastname: Moutinho-Santos
authors.forename: Diana
authors.initials: D
authors.lastname: Pinheiro
authors.forename: Sofia
authors.initials: S
authors.lastname: Guimarães
authors.forename: Irina
authors.initials: I
authors.lastname: Matos
authors.forename: Helder
authors.initials: H
authors.lastname: Maiato
authors.forename: Claudio E
authors.initials: CE
authors.lastname: Sunkel
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D018386:Kinetochores / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*
chemical_list: C506005:BubR1 protein, Drosophila; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C577502:fzy protein, Drosophila; C072004:polo protein, Drosophila; D064127:Aurora Kinases; C501876:Mps1 protein, Drosophila; D017346:Protein Serine-Threonine Kinases