title: CELL DIVISION CYCLE. Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling.
abstract: Cell division progresses to anaphase only after all chromosomes are connected to spindle microtubules through kinetochores and the spindle assembly checkpoint (SAC) is satisfied. We show that the amino-terminal localization module of the SAC protein kinase MPS1 (monopolar spindle 1) directly interacts with the HEC1 (highly expressed in cancer 1) calponin homology domain in the NDC80 (nuclear division cycle 80) kinetochore complex in vitro, in a phosphorylation-dependent manner. Microtubule polymers disrupted this interaction. In cells, MPS1 binding to kinetochores or to ectopic NDC80 complexes was prevented by end-on microtubule attachment, independent of known kinetochore protein-removal mechanisms. Competition for kinetochore binding between SAC proteins and microtubules provides a direct and perhaps evolutionarily conserved way to detect a properly organized spindle ready for cell division.
authors.affiliation: Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hiruma
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sacristan
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands.
authors.forename: Spyridon T
authors.initials: ST
authors.lastname: Pachis
authors.affiliation: Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Adamopoulos
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands.
authors.forename: Timo
authors.initials: T
authors.lastname: Kuijt
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Post Office Box 9502, 2300 RA Leiden, Netherlands.
authors.forename: Marcellus
authors.initials: M
authors.lastname: Ubbink
authors.affiliation: Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Eleonore
authors.initials: E
authors.lastname: von Castelmur
authors.affiliation: Division of Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. g.j.p.l.kops@umcutrecht.nl a.perrakis@nki.nl.
authors.forename: Anastassis
authors.initials: A
authors.lastname: Perrakis
authors.affiliation: Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. Cancer Genomics Netherlands, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands. g.j.p.l.kops@umcutrecht.nl a.perrakis@nki.nl.
authors.forename: Geert J P L
authors.initials: GJ
authors.lastname: Kops
mesh_terms: D000705:Anaphase; D001667:Binding, Competitive; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism*; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000096985:Calponins; C120529:NDC80 protein, human; C075840:TTK protein, human