Silencing the spindle assembly checkpoint: Let's play Polo!

Abstract

Silencing of the spindle assembly checkpoint involves two protein phosphatases, PP1 and PP2A-B56, that are thought to extinguish checkpoint signaling through dephosphorylation of a checkpoint scaffold at kinetochores. In this issue, Cordeiro et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.202002020) now show that a critical function of these phosphatases in checkpoint silencing is removal of Polo kinase at kinetochores, which would otherwise autonomously sustain the checkpoint.

Figure 1.

The interplay of SAC kinases and phosphatases at kinetochores. When SAC is activated at an unattached kinetochore (SAC on), MPS1 phosphorylates the kinetochore scaffold KNL1, thereby recruiting the BUB complex. Contextually, CDK1-dependent phosphorylation of BUB1 and BUBR1 generates phospho-docking sites for recruitment of the Polo kinase PLK1, which on one side sustains KNL1 phosphorylation and on the other stimulates BUBR1 binding to PP2A-B56. The latter, in turn, counteracts PLK1 local activity by dislodging PLK1 from the kinetochore. During SAC silencing, local activity of MPS1 is shut off. Additionally, the PP1 phosphatase binds to KNL1 and, together with PP2A-B56, further evicts PLK1 from the kinetochore, possibly through dephosphorylation of its phospho-docking sites in BUB1 and BUBR1. This leads to KNL1 dephosphorylation and displacement of the BUB complex, thus extinguishing SAC signaling (SAC off). Whether PP1 and PP2A-B56, as opposed to other phosphatases, contribute directly to KNL1 dephosphorylation remains an open question.