PKC? switches Aurora B specificity to exit the abscission checkpoint.

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

SUBMITTER: Pike T 

PROVIDER: S-EPMC5192180 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature