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The spindle assembly checkpoint (SAC) monitors correct attachment of chromosomes to microtubules, an important safeguard mechanism ensuring faithful chromosome segregation in eukaryotic cells. How the SAC signal is turned off once all the chromosomes have successfully attached to the spindle remains an unresolved question. Mps1 phosphorylation of Knl1 results in recruitment of the SAC proteins Bub1, Bub3, and BubR1 to the kinetochore and production of the wait-anaphase signal. SAC silencing is therefore expected to involve a phosphatase opposing Mps1. Here we demonstrate in vivo and in vitro that BubR1-associated PP2A-B56 is a key phosphatase for the removal of the Mps1-mediated Knl1 phosphorylations necessary for Bub1/BubR1 recruitment in mammalian cells. SAC silencing is thus promoted by a negative feedback loop involving the Mps1-dependent recruitment of a phosphatase opposing Mps1. Our findings extend the previously reported role for BubR1-associated PP2A-B56 in opposing Aurora B and suggest that BubR1-bound PP2A-B56 integrates kinetochore surveillance and silencing of the SAC.

Original publication

DOI

10.1083/jcb.201406109

Type

Journal article

Journal

J Cell Biol

Publication Date

29/09/2014

Volume

206

Pages

833 - 842

Keywords

Cell Cycle Proteins, HeLa Cells, Humans, Kinetochores, M Phase Cell Cycle Checkpoints, Microtubule-Associated Proteins, Phosphorylation, Protein Phosphatase 2, Protein Processing, Post-Translational, Protein Transport, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases