title: Plk1 and Mps1 Cooperatively Regulate the Spindle Assembly Checkpoint in Human Cells.
abstract: Equal mitotic chromosome segregation is critical for genome integrity and is monitored by the spindle assembly checkpoint (SAC). We have previously shown that the consensus phosphorylation motif of the essential SAC kinase Monopolar spindle 1 (Mps1) is very similar to that of Polo-like kinase 1 (Plk1). This prompted us to ask whether human Plk1 cooperates with Mps1 in SAC signaling. Here, we demonstrate that Plk1 promotes checkpoint signaling at kinetochores through the phosphorylation of at least two Mps1 substrates, including KNL-1 and Mps1 itself. As a result, Plk1 activity enhances Mps1 catalytic activity as well as the recruitment of the SAC components Mad1:C-Mad2 and Bub3:BubR1 to kinetochores. We conclude that Plk1 strengthens the robustness of SAC establishment at the onset of mitosis and supports SAC maintenance during prolonged mitotic arrest.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Conrad
authors.initials: C
authors.lastname: von Schubert
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Fabien
authors.initials: F
authors.lastname: Cubizolles
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Bracher
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands; Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
authors.forename: Tale
authors.initials: T
authors.lastname: Sliedrecht
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands; Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands; Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG, Utrecht, the Netherlands.
authors.forename: Geert J P L
authors.initials: GJPL
authors.lastname: Kops
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland. Electronic address: erich.nigg@unibas.ch.
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C489444:BUB3 protein, human; C472643:Knl1 protein, human; C501384:MAD1L1 protein, human; C577697:MAD2L1 protein, human; C584277:BUB1 protein, human; C075840:TTK protein, human