Journal
NATURE CELL BIOLOGY
Volume 13, Issue 10, Pages 1265-U216Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2327
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Funding
- Damon Runyon Cancer Research postdoctoral fellowship [DRG 1936-07]
- Charles H. Revson Foundation
- NIH [GM65933]
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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 destabilization(2-7). 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 attachments(2,8). 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 suppressor(9), tunes the balance of phosphorylation to promote chromosome-spindle interactions during cell division.
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