PKCϵ switches Aurora B specificity to exit the abscission checkpoint

TY - JOUR

T1 - PKCϵ switches Aurora B specificity to exit the abscission checkpoint

AU - Pike, Tanya

AU - Brownlow, Nicola

AU - Kjaer, Svend

AU - Carlton, Jeremy

AU - Parker, Peter J.

PY - 2016/12/22

Y1 - 2016/12/22

N2 - 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 PKCIϵ in transformed cell models. Here we show that PKCIϵ 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 PKCIϵ -Aurora B exit pathway. Thus, we demonstrate that PKCIϵ signals through Aurora B to exit the abscission checkpoint and complete cell division.

AB - 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 PKCIϵ in transformed cell models. Here we show that PKCIϵ 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 PKCIϵ -Aurora B exit pathway. Thus, we demonstrate that PKCIϵ signals through Aurora B to exit the abscission checkpoint and complete cell division.

UR - http://www.scopus.com/inward/record.url?scp=85007007361&partnerID=8YFLogxK

U2 - 10.1038/ncomms13853

DO - 10.1038/ncomms13853

M3 - Article

AN - SCOPUS:85007007361

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 13853

ER -