PKCɛ switches Aurora B specificity to exit the abscission checkpoint
Tanya Pike,
Nicola Brownlow,
Svend Kjaer,
Jeremy Carlton and
Peter J. Parker ()
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Tanya Pike: Protein Phosphorylation Laboratory, The Francis Crick Institute
Nicola Brownlow: Protein Phosphorylation Laboratory, The Francis Crick Institute
Svend Kjaer: Protein Purification Facility, Francis Crick Institute
Jeremy Carlton: Division of Cancer Studies King’s College London
Peter J. Parker: Protein Phosphorylation Laboratory, The Francis Crick Institute
Nature Communications, 2016, vol. 7, issue 1, 1-10
Abstract:
Abstract The ‘NoCut’, or Aurora B abscission checkpoint can be activated if DNA is retained in the cleavage furrow after completion of anaphase. Checkpoint failure leads to incomplete abscission and a binucleate outcome. These phenotypes are also observed after loss of PKCɛ in transformed cell models. Here we show that PKCɛ directly modulates the Aurora B-dependent abscission checkpoint by phosphorylating Aurora B at S227. This phosphorylation invokes a switch in Aurora B specificity, with increased phosphorylation of a subset of target substrates, including the CPC subunit Borealin. This switch is essential for abscission checkpoint exit. Preventing the phosphorylation of Borealin leads to abscission failure, as does expression of a non-phosphorylatable Aurora B S227A mutant. Further, depletion of the ESCRT-III component and Aurora B substrate CHMP4C enables abscission, bypassing the PKCɛ–Aurora B exit pathway. Thus, we demonstrate that PKCɛ signals through Aurora B to exit the abscission checkpoint and complete cell division.
Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13853
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DOI: 10.1038/ncomms13853
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