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Review
. 2020 Dec:78:100759.
doi: 10.1016/j.jbior.2020.100759. Epub 2020 Oct 7.

A cancer-associated, genome protective programme engaging PKCε

Peter J Parker  1 , Nicola Lockwood  2 , Khalil Davis  2 , Joanna R Kelly  3 , Tanya N Soliman  4 , Ainara Lopez Pardo  2 , Jacqueline J T Marshall  2 , Joanna M Redmond  5 , Marco Vitale  6 , Silvia Martini  2
Affiliations
Review

A cancer-associated, genome protective programme engaging PKCε

Peter J Parker et al. Adv Biol Regul. 2020 Dec.

Abstract

Associated with their roles as targets for tumour promoters, there has been a long-standing interest in how members of the protein kinase C (PKC) family act to modulate cell growth and division. This has generated a great deal of observational data, but has for the most part not afforded clear mechanistic insights into the control mechanisms at play. Here, we review the roles of PKCε in protecting transformed cells from non-disjunction. In this particular cell cycle context, there is a growing understanding of the pathways involved, affording biomarker and interventional insights and opportunities.

Keywords: Aurora B; Cell cycle; Non-disjunction; PKCe.

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Conflict of interest statement

None.

PJP drafted the manuscript and all authors added information, revised sections and edited the final version.

Figures

Fig. 1
Fig. 1
Organisation of PKCε. A schematic diagram is shown of the domains of PKCε from the N-terminus (top) through the C2 domain, pseudosubstrate site (PSS), C1A domain, inter C1 domain region (IC1D), C1B domain, variable 3 region (V3) and C-terminal Kinase domain (Kin). Interacting ligands germane to the review are indicated; specifically, diacylglycerol (DAG) in a membrane compartment, 14-3-3, autoinhibition with the PSS binding the kinase domain substrate site (----). Post-translational events discussed in the text are illustrated alongside their effectors (kinases/target sites and protease/cleavage sites). Canonical and non-canonical activation pathways are indicated and colour coded. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Fig. 2
Fig. 2
PKCε action in transformed cells. The Topo2-dependent arrest in G2 is indicated diagrammatically in the context of a normal cell cycle. The switch to a PKCε-dependent pathway (red) occurs in cells failing to arrest (see text). This leads to a series of delays under the control of PKCε as indicated. These are implemented by distinct mechanisms (see text for a more detailed discussion). Resolution of non-disjunction stress enables the maintenance of chromosomal integrity and the completion of division; failure to resolve produces division failure and/or chromosome damage. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
See this image and copyright information in PMC

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