title: PKCɛ 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 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.
authors.affiliation: Protein Phosphorylation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Tanya
authors.initials: T
authors.lastname: Pike
authors.affiliation: Protein Phosphorylation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Brownlow
authors.affiliation: Protein Purification Facility, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Svend
authors.initials: S
authors.lastname: Kjaer
authors.affiliation: Division of Cancer Studies King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Carlton
authors.affiliation: Protein Phosphorylation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.|Division of Cancer Studies King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Parker
mesh_terms: D000595:Amino Acid Sequence; D000705:Anaphase; D064107:Aurora Kinase B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D048749:Cytokinesis; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: C490157:CDCA8 protein, human; C541008:CHMP4C protein, human; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D011994:Recombinant Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon