CELL DIVISION CYCLE. Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling

Science. 2015 Jun 12;348(6240):1264-7. doi: 10.1126/science.aaa4055. Epub 2015 Jun 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase
  • Binding, Competitive
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Cycle Checkpoints*
  • Cell Cycle Proteins / metabolism*
  • Cytoskeletal Proteins
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microtubules / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Spindle Apparatus / metabolism*

Substances

  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Microfilament Proteins
  • NDC80 protein, human
  • Nuclear Proteins
  • calponin
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • TTK protein, human