Kinetochore phosphatases suppress autonomous Polo-like kinase 1 activity to control the mitotic checkpoint

Marilia H. Cordeiro (Lead / Corresponding author), Richard J. Smith, Adrian T. Saurin (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

42 Downloads (Pure)

Abstract

Local phosphatase regulation is needed at kinetochores to silence the mitotic checkpoint (a.k.a. spindle assembly checkpoint [SAC]). A key event in this regard is the dephosphorylation of MELT repeats on KNL1, which removes SAC proteins from the kinetochore, including the BUB complex. We show here that PP1 and PP2A-B56 phosphatases are primarily required to remove Polo-like kinase 1 (PLK1) from the BUB complex, which can otherwise maintain MELT phosphorylation in an autocatalytic manner. This appears to be their principal role in the SAC because both phosphatases become redundant if PLK1 is inhibited or BUB–PLK1 interaction is prevented. Surprisingly, MELT dephosphorylation can occur normally under these conditions even when the levels or activities of PP1 and PP2A are strongly inhibited at kinetochores. Therefore, these data imply that kinetochore phosphatase regulation is critical for the SAC, but primarily to restrain and extinguish autonomous PLK1 activity. This is likely a conserved feature of the metazoan SAC, since the relevant PLK1 and PP2A-B56 binding motifs have coevolved in the same region on MADBUB homologues.
Original languageEnglish
Article numbere202002020
Number of pages27
JournalJournal of Cell Biology
Volume219
Issue number12
Early online date30 Oct 2020
DOIs
Publication statusE-pub ahead of print - 30 Oct 2020

Keywords

  • Cell cycle and division
  • Cell signaling

Fingerprint Dive into the research topics of 'Kinetochore phosphatases suppress autonomous Polo-like kinase 1 activity to control the mitotic checkpoint'. Together they form a unique fingerprint.

Cite this