title: Phosphorylation regulates the p31Comet-mitotic arrest-deficient 2 (Mad2) interaction to promote spindle assembly checkpoint (SAC) activity.
abstract: The spindle assembly checkpoint (SAC) ensures the faithful segregation of the genome during mitosis by ensuring that sister chromosomes form bipolar attachments with microtubules of the mitotic spindle. p31(Comet) is an antagonist of the SAC effector Mad2 and promotes silencing of the SAC and mitotic progression. However, p31(Comet) interacts with Mad2 throughout the cell cycle. We show that p31(Comet) binds Mad2 solely in an inhibitory manner. We demonstrate that attenuating the affinity of p31(Comet) for Mad2 by phosphorylation promotes SAC activity in mitosis. Specifically, phosphorylation of Ser-102 weakens p31(Comet)-Mad2 binding and enhances p31(Comet)-mediated bypass of the SAC. Our results provide the first evidence for regulation of p31(Comet) and demonstrate a previously unknown event controlling SAC activity.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio 44195.
authors.forename: Dipali A
authors.initials: DA
authors.lastname: Date
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio 44195.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Burrows
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland, Ohio 44195. Electronic address: summerm@ccf.org.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Summers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology*; D064246:Mad2 Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; C470309:MAD2L1BP protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins
keywords: Anaphase-promoting Complex; Cell Cycle; Cell Division; Mad2; Mitosis; Mitotic Checkpoint Complex; Protein Complexes; Protein Phosphorylation; Spindle Assembly Checkpoint; p31Comet