Mitotic kinase CDK1 cooperates with polo kinase to ensure the temporal regulation of kinetochore microtubule dynamics and spindle checkpoint (802.14)

Abstract

Chromosome movements during mitosis are orchestrated primarily by the interaction of spindle microtubules with the kinetochore, the site for attachment of spindle microtubules to the centromere, at which mitotic kinase circuitry synergized to ensure the quality control of cell division. Mitotic master kinase Cdk1 controls many aspects of mitotic chromosome behavior and spindle microtubule dynamics to ensure accurate chromosome segregation. Polo kinase 1 (PLK1) is a highly conserved mitotic kinase and activation of PLK1 requires phosphorylation of the T‐loop. Here we show that phosphorylation of PLK1 T‐loop by CDK1 in conserved Thr214 is essential for temporal control of kinetochore microtubule dynamics and spindle checkpoint signaling. Phosphorylates PLK1 at Thr214 suppresses microtubule dynamics and promotes the stabilization of initial kinetochore‐microtubule attachments in prometaphase. Using fluorescence resonance energy transfer‐based reporter of PLK1 activity at the kinetochore and quantitative analysis of native PLK1 substrate phosphorylation, we show that constitutively phosphorylation of Thr214 reduces inter‐kinetochore tension and turnover of kinetochore microtubules, resulting in increased microtubule attachment errors and a checkpoint dependent mitotic arrest. Therefore, we reason that phosphorylation of PLK1 by CDK1 is essential to ensure the temporal regulation of kinetochore microtubule dynamics and spindle checkpoint control.Grant Funding Source: DK56292; CA164133