Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosph

Abstract

The microtubules that attach kinetochores to chromosomes (K-fibres) are stabilized in prometaphase to allow for accurate chromosome segregation. Kapoor and colleagues find that the B56-PP2A phosphatase stabilizes K-fibres potentially by counteracting the phosphorylation of kinetochore substrates that is mediated by Aurora B and Plk1. Error-free chromosome segregation depends on the precise regulation of phosphorylation to stabilize kinetochore–microtubule attachments (K-fibres) on sister chromatids that have attached to opposite spindle poles (bi-oriented)1. In many instances, phosphorylation correlates with K-fibre destabilization2,3,4,5,6,7. Consistent with this, multiple kinases, including Aurora B and Plk1, are enriched at kinetochores of mal-oriented chromosomes when compared with bi-oriented chromosomes, which have stable attachments2,8. Paradoxically, however, these kinases also target to prometaphase chromosomes that have not yet established spindle attachments and it is therefore unclear how kinetochore–microtubule interactions can be stabilized when kinase levels are high. Here we show that the generation of stable K-fibres depends on the B56-PP2A phosphatase, which is enriched at centromeres/kinetochores of unattached chromosomes. When B56-PP2A is depleted, K-fibres are destabilized and chromosomes fail to align at the spindle equator. Strikingly, B56-PP2A depletion increases the level of phosphorylation of Aurora B and Plk1 kinetochore substrates as well as Plk1 recruitment to kinetochores. Consistent with increased substrate phosphorylation, we find that chemical inhibition of Aurora or Plk1 restores K-fibres in B56-PP2A-depleted cells. Our findings reveal that PP2A, an essential tumour suppressor9, tunes the balance of phosphorylation to promote chromosome–spindle interactions during cell division.

Cite this article

Foley, E., Maldonado, M. & Kapoor, T. Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase. Nat Cell Biol 13, 1265–1271 (2011). https://doi.org/10.1038/ncb2327

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