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Co-ordinated control of the Aurora B abscission checkpoint by PKCϵ complex assembly, midbody recruitment and retention

Research output: Contribution to journalArticlepeer-review

Lisa Watson, Tanya N. Soliman, Khalil Davis, Joanna Kelly, Nicola Lockwood, Xiaoping Yang, Steven Lynham, John D. Scott, Victoria Crossland, Neil Q. McDonald, David J. Mann, Alan Armstrong, Ulrike Eggert, Peter J. Parker

Original languageEnglish
Pages (from-to)2247-2263
Number of pages17
JournalBiochemical Journal
Volume478
Issue number12
DOIs
PublishedJun 2021

Bibliographical note

Funding Information: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research U. K. (FC001130), the U.K. Medical Research Council (FC001130) and the Wellcome Trust (FC001130). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. JDS is supported by NIH grant DK119186. Publisher Copyright: © 2021 The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

A requirement for PKCϵ in exiting from the Aurora B dependent abscission checkpoint is associated with events at the midbody, however, the recruitment, retention and action of PKCϵ in this compartment are poorly understood. Here, the prerequisite for 14-3-3 complex assembly in this pathway is directly linked to the phosphorylation of Aurora B S227 at the midbody. However, while essential for PKCϵ control of Aurora B, 14-3-3 association is shown to be unnecessary for the activity-dependent enrichment of PKCϵ at the midbody. This localisation is demonstrated to be an autonomous property of the inactive PKCϵ D532N mutant, consistent with activity-dependent dissociation. The C1A and C1B domains are necessary for this localisation, while the C2 domain and inter-C1 domain (IC1D) are necessary for retention at the midbody. Furthermore, it is shown that while the IC1D mutant retains 14-3-3 complex proficiency, it does not support Aurora B phosphorylation, nor rescues division failure observed with knockdown of endogenous PKCϵ. It is concluded that the concerted action of multiple independent events facilitates PKCϵ phosphorylation of Aurora B at the midbody to control exit from the abscission checkpoint.

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