title: RINGO C is required to sustain the spindle-assembly checkpoint.
abstract: RINGO/Speedy proteins are direct activators of Cdk1 and Cdk2 that have no sequence homology to cyclins. We have characterized the role in cell-cycle progression of a new human member of this protein family referred to as RINGO C. We show that siRNA-mediated knockdown of RINGO C results in premature mitotic exit with misaligned chromosomes, even in the presence of microtubule poisons. Time-lapse-microscopy experiments suggest that RINGO C is involved in the spindle-assembly checkpoint (SAC). Consistent with this idea, RINGO-C-depleted cells show impaired recruitment of the SAC components Mad2, Bub1 and BubR1. As the checkpoint is overridden, cells display defective chromosome segregation, which leads to an increased number of micronuclei and binucleated structures. Intriguingly, we found that RINGO C can associate with the mitotic kinase Aurora B, and downregulation of RINGO C produces mislocalization of the active form of Aurora B in prometaphase. Taken together, our results indicate a role for RINGO C in the mitotic checkpoint, which might be mediated by defective recruitment of SAC components and deregulation of the activity of Aurora kinase B.
authors.affiliation: Signalling and Cell Cycle Group, CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: Silvana
authors.initials: S
authors.lastname: Mourón
authors.forename: Guillermo
authors.initials: G
authors.lastname: de Cárcer
authors.forename: Esther
authors.initials: E
authors.lastname: Seco
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Fernández-Miranda
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
authors.forename: Angel R
authors.initials: AR
authors.lastname: Nebreda
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D018386:Kinetochores / Q000378:metabolism; D008677:Metaphase / Q000187:drug effects / Q000235:genetics; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; C486530:SPDYA protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D015739:Nocodazole