Whyteside, A.R., Turner, A.J. and Lambert, D.W. orcid.org/0000-0001-9003-3145 (2014) Endothelin-Converting Enzyme-1 (ECE-1) Is Post-Transcriptionally Regulated by Alternative Polyadenylation. PLOS One, 9 (1). e83260. ISSN 1932-6203
Abstract
Endothelin-converting enzyme-1 (ECE-1) is the enzyme predominantly responsible for producing active endothelin-1 (ET-1), a mitogenic peptide implicated in the aetiology of a number of diseases, including cancer. Elevated levels of ECE-1 have been observed in a range of malignancies, with high expression conferring poor prognosis and aiding the acquisition of androgen independence in prostate cancer. The mechanisms regulating the expression of ECE-1 in cancer cells are poorly understood, hampering the development of novel therapies targeting the endothelin axis. Here we provide evidence that the expression of ECE-1 is markedly inhibited by its 3′UTR, and that alternative polyadenylation (APA) results in the production of ECE-1 transcripts with truncated 3′UTRs which promote elevated protein expression. Abolition of the ECE-1 APA sites reduced protein expression from a reporter vector in prostate cancer cells, suggesting these sites are functional. This is the first study to identify ECE-1 as a target for APA, a regulatory mechanism aberrantly activated in cancer cells, and provides novel information about the mechanisms leading to ECE-1 overexpression in malignant cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 Whyteside et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Mar 2016 13:26 |
Last Modified: | 29 Mar 2016 13:26 |
Published Version: | http://dx.doi.org/10.1371/journal.pone.0083260 |
Status: | Published |
Publisher: | Public Library of Science |
Refereed: | Yes |
Identification Number: | 10.1371/journal.pone.0083260 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:96961 |