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

• Plk1 promotes the spindle checkpoint through a substrate preference shared with Mps1
• Plk1 and Mps1 cooperatively phosphorylate KNL-1 MELT motifs and Mps1
• Plk1 potentiates Bub3:BubR1 and Mad1:C-Mad2 kinetochore recruitment and Mps1 activity

SummaryEqual 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.

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