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Endothelin-converting enzyme-1 (ECE-1) is post-transcriptionally regulated by alternative polyadenylation.


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.

SUBMITTER: Whyteside AR 

PROVIDER: S-EPMC3908869 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Endothelin-converting enzyme-1 (ECE-1) is post-transcriptionally regulated by alternative polyadenylation.

Whyteside Alison R AR   Turner Anthony J AJ   Lambert Daniel W DW  

PloS one 20140131 1


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, hamperin  ...[more]

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