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Grant support

This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001130), the UK Medical Research Council (FC001130) and the Wellcome Trust (FC001130). We thank all of the Francis Crick Institute core facilities for valuable support throughout this project, in particular the light microscopy, peptide synthesis and protein production facility. We also thank Stephen Taylor for kindly supplying the tetracycline inducible DLD1 cell line. We acknowledge Dr Mark Petronczski for providing the Aurora B construct, Dr Jon Elkins for the Aurora B construct to produce the recombinant protein and we thank both for their helpful advice and discussions. Thanks also to Drs Katharina Deiss and Philippe Riou for critical reading of the manuscript.

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March 25, 2020
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Article

PKCɛ switches Aurora B specificity to exit the abscission checkpoint

Publicated to:Nature Communications. 7 13853- - 2016-12-22 7(), DOI: 10.1038/ncomms13853

Authors: Pike, T; Brownlow, N; Kjaer, S; Carlton, J; Parker, PJ

Affiliations

Ctr Genom Regulat CRG, Dr Aiguader 88,PRBB Bldg, Barcelona 08003, Spain - Author
Francis Crick Inst, Prot Phosphorylat Lab, 1 Midland Rd, London NW1 1AT, England - Author
Francis Crick Inst, Prot Purificat Facil, 1 Midland Rd, London NW1 1AT, England - Author
Kings Coll London, Div Canc Studies, New Hunts House,Guys Campus, London SE1 1UL, England - Author
Protein Phosphorylation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.;Protein Phosphorylation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.;Protein Purification Facility, 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.;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. - Author
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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.

Keywords

BorealinCompletionCytokinesisEscrtMidbodyPhosphorylationProtein-kinase-cSpindleStability

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Communications due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2016, it was in position 3/63, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.48, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-02, the following number of citations:

  • WoS: 22
  • Scopus: 13
  • Europe PMC: 17

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 53.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 53 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.5.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United Kingdom.