Plk1 and Mps1 Cooperatively Regulate the Spindle Assembly Checkpoint in Human Cells

Cell Rep. 2015 Jul 7;12(1):66-78. doi: 10.1016/j.celrep.2015.06.007. Epub 2015 Jun 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Humans
  • M Phase Cell Cycle Checkpoints*
  • Mad2 Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Poly-ADP-Ribose Binding Proteins
  • Protein Binding
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Spindle Apparatus / metabolism

Substances

  • BUB3 protein, human
  • Cell Cycle Proteins
  • Knl1 protein, human
  • MAD1L1 protein, human
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • BUB1 protein, human
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • TTK protein, human