Abstract
The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states. The molecular regulation of COX-2 gene expression is normally tightly regulated on transcriptional and post-transcriptional levels. However, loss of function at either level of COX-2 gene regulation promotes constitutive COX-2 overexpression which plays a key role in carcinogenesis, particularly colorectal tumorigenesis. Current work investigating the regulatory mechanisms of COX-2 expression has demonstrated post-transcriptional regulation to play a central role. Rapid COX-2 mRNA decay and translational inhibition is mediated through a conserved AU-rich element (ARE) present within the 3-untranslated region (3UTR). The COX-2 ARE exerts its control through association with ARE RNA-binding proteins. These trans-acting regulatory factors influence the fate of COX-2 mRNA by controlling mRNA degradation, stabilization, or translation. Recent evidence demonstrates the functional significance rapid mRNA decay and translational inhibition play in controlling COX-2 gene expression and that, if dysregulated, allow for overexpression of COX-2 and other associated angiogenic factors detected in neoplasia.
Keywords: cox, cyclooxygenase, prostaglandins, cancer, post-transcriptional regulation, mrna stability, au-rich element, rna-binding protein
Current Pharmaceutical Design
Title: Dysregulated Post-Transcriptional Control of COX-2 Gene Expression in Cancer
Volume: 10 Issue: 6
Author(s): Dan A. Dixon
Affiliation:
Keywords: cox, cyclooxygenase, prostaglandins, cancer, post-transcriptional regulation, mrna stability, au-rich element, rna-binding protein
Abstract: The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states. The molecular regulation of COX-2 gene expression is normally tightly regulated on transcriptional and post-transcriptional levels. However, loss of function at either level of COX-2 gene regulation promotes constitutive COX-2 overexpression which plays a key role in carcinogenesis, particularly colorectal tumorigenesis. Current work investigating the regulatory mechanisms of COX-2 expression has demonstrated post-transcriptional regulation to play a central role. Rapid COX-2 mRNA decay and translational inhibition is mediated through a conserved AU-rich element (ARE) present within the 3-untranslated region (3UTR). The COX-2 ARE exerts its control through association with ARE RNA-binding proteins. These trans-acting regulatory factors influence the fate of COX-2 mRNA by controlling mRNA degradation, stabilization, or translation. Recent evidence demonstrates the functional significance rapid mRNA decay and translational inhibition play in controlling COX-2 gene expression and that, if dysregulated, allow for overexpression of COX-2 and other associated angiogenic factors detected in neoplasia.
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Cite this article as:
Dixon A. Dan, Dysregulated Post-Transcriptional Control of COX-2 Gene Expression in Cancer, Current Pharmaceutical Design 2004; 10 (6) . https://dx.doi.org/10.2174/1381612043453171
DOI https://dx.doi.org/10.2174/1381612043453171 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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