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RACK1 stabilises the activity of PP2A to regulate the transformed phenotype in mammary epithelial cells

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Show simple item record Kiely, Maeve Adams, David R. Hayes, Sheri L. O'Connor, Rosemary Baillie, George S. Kiely, Patrick A. 2018-11-21T16:03:34Z 2018-11-21T16:03:34Z 2017
dc.description peer-reviewed en_US
dc.description.abstract Conflicting reports implicate the scaffolding protein RACK1 in the progression of breast cancer. RACK1 has been identified as a key regulator downstream of growth factor and adhesion signalling and as a direct binding partner of PP2A. Our objective was to further characterise the interaction between PP2A and RACK1 and to advance our understanding of this complex in breast cancer cells. We examined how the PP2A holoenzyme is assembled on the RACK1 scaffold in MCF-7 cells. We used immobilized peptide arrays representing the entire PP2A-catalytic subunit to identify candidate amino acids on the C subunit of PP2A that might be involved in binding of RACK1. We identified the RACK1 interaction sites on PP2A. Stable cell lines expressing PP2A with FR69/70AA, R214A and Y218F substitutions were generated and it was confirmed that the RACK1/PP2A interaction is essential to stabilise PP2A activity. We used Real-Time Cell Analysis and a series of assays to demonstrate that disruption of the RACK1/PP2A complex also reduces the adhesion, proliferation, migration and invasion of breast cancer cells and plays a role in maintenance of the cancer phenotype. This work has significantly advanced our understanding of the RACK1/PP2A complex and suggests a pro-carcinogenic role for the RACK1/PP2A interaction. This work suggests that approaches to target the RACK1/PP2A complex are a viable option to regulate PP2A activity and identifies a novel potential therapeutic target in the treatment of breast cancer. (C) 2016 Elsevier Inc All rights reserved. en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation 13/CDA/2228 en_US
dc.relation.ispartofseries Cellular Signalling: 35, pp. 290-300
dc.rights This is the author’s version of a work that was accepted for publication in Cellular Signalling. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cellular Signalling, 2017, 35, pp. 290-300, en_US
dc.subject Breast cancer en_US
dc.subject RACK1 en_US
dc.subject PP2A en_US
dc.subject Protein-protein interactions en_US
dc.title RACK1 stabilises the activity of PP2A to regulate the transformed phenotype in mammary epithelial cells en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US 2018-11-21T15:53:01Z
dc.description.version ACCEPTED
dc.identifier.doi 10.1016/j.cellsig.2016.09.001
dc.contributor.sponsor SFI en_US
dc.contributor.sponsor Irish Cancer Society en_US
dc.relation.projectid 13/CDA/2228 en_US
dc.relation.projectid CRS11KIE en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 2715985
dc.internal.copyrightchecked Yes
dc.identifier.journaltitle Cellular signalling
dc.description.status peer-reviewed

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