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Nucleic Acids Research Advance Access originally published online on October 12, 2006
Nucleic Acids Research 2006 34(19):5705-5714; doi:10.1093/nar/gkl698
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Nucleic Acids Research, 2006, Vol. 34, No. 19 5705-5714
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

ß-Catenin stabilizes Cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3'-UTR

Hee Kyu Lee and Sunjoo Jeong*

Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Institute of Nanosensor and Biotechnology, Dankook University Seoul 140-714, Republic of Korea

*To whom correspondence should be addressed. Tel: +82 2 709 2819; Fax: +82 2 793 0176; Email: sjsj{at}dankook.ac.kr

Received August 3, 2006. Revised September 8, 2006. Accepted September 8, 2006.

Cyclooxygenase-2 (COX-2) mRNA is induced in the majority of human colorectal carcinomas. Transcriptional regulation plays a key role in COX-2 expression in human colon carcinoma cells, but post-transcriptional regulation of its mRNA is also critical for tumorigenesis. Expression of COX-2 mRNA is regulated by various cytokines, growth factors and other signals. ß-Catenin, a key transcription factor in the Wnt signal pathway, activates transcription of COX-2. Here we found that COX-2 mRNA was also substantially stabilized by activating ß-catenin in NIH3T3 and 293T cells. We identified the ß-catenin-responsive element in the proximal region of the COX-2 3'-untranslated region (3'-UTR) and showed that ß-catenin interacted with AU-rich elements (ARE) of 3'-UTR in vitro and in vivo. Interestingly, ß-catenin induced the cytoplasmic localization of the RNA stabilizing factor, HuR, which may bind to ß-catenin in an RNA-mediated complex and facilitate ß-catenin-dependent stabilization of COX-2 mRNA. Taken together, we provided evidences for ß-catenin as an RNA-binding factor and a regulator of stabilization of COX-2 mRNA.


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