TY - JOUR TI - Cyclin A/Cdk1 modulates Plk1 activity in prometaphase to regulate kinetochore-microtubule attachment stability AU - Dumitru, Ana Maria G AU - Rusin, Scott F AU - Clark, Amber E M AU - Kettenbach, Arminja N AU - Compton, Duane A A2 - Cleveland, Don W VL - 6 PY - 2017 DA - 2017/11/20 SP - e29303 C1 - eLife 2017;6:e29303 DO - 10.7554/eLife.29303 UR - https://doi.org/10.7554/eLife.29303 AB - The fidelity of chromosome segregation in mitosis is safeguarded by the precise regulation of kinetochore microtubule (k-MT) attachment stability. Previously, we demonstrated that Cyclin A/Cdk1 destabilizes k-MT attachments to promote faithful chromosome segregation. Here, we use quantitative phosphoproteomics to identify 156 Cyclin A/Cdk1 substrates in prometaphase. One Cyclin A/Cdk1 substrate is myosin phosphatase targeting subunit 1 (MYPT1), and we show that MYPT1 localization to kinetochores depends on Cyclin A/Cdk1 activity and that MYPT1 destabilizes k-MT attachments by negatively regulating Plk1 at kinetochores. Thus, Cyclin A/Cdk1 phosphorylation primes MYPT1 for Plk1 binding. Interestingly, priming of PBIP1 by Plk1 itself (self-priming) increased in MYPT1-depleted cells showing that MYPT1 provides a molecular link between the processes of Cdk1-dependent priming and self-priming of Plk1 substrates. These data demonstrate cross-regulation between Cyclin A/Cdk1-dependent and Plk1-dependent phosphorylation of substrates during mitosis to ensure efficient correction of k-MT attachment errors necessary for high mitotic fidelity. KW - mitosis KW - kinetochore KW - Plk1 KW - microtubule KW - cyclin dependent kinase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -