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PMID: 17040897 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3'-UTR.

Nucleic acids research ·Vol. 34 ·No. 19 ·2006-00-00 ·Pages 5705-14

Lee HK, Jeong S

Abstract

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. beta-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 beta-catenin in NIH3T3 and 293T cells. We identified the beta-catenin-responsive element in the proximal region of the COX-2 3'-untranslated region (3'-UTR) and showed that beta-catenin interacted with AU-rich elements (ARE) of 3'-UTR in vitro and in vivo. Interestingly, beta-catenin induced the cytoplasmic localization of the RNA stabilizing factor, HuR, which may bind to beta-catenin in an RNA-mediated complex and facilitate beta-catenin-dependent stabilization of COX-2 mRNA. Taken together, we provided evidences for beta-catenin as an RNA-binding factor and a regulator of stabilization of COX-2 mRNA.

MeSH Terms
3' Untranslated Regions/chemistry,metabolism Adenine/analysis Animals Antigens, Surface/metabolism Base Sequence Binding Sites Cell Line Cyclooxygenase 2/genetics,metabolism ELAV Proteins ELAV-Like Protein 1 Gene Expression Regulation, Enzymologic Humans Mice RNA Stability RNA, Messenger/metabolism RNA-Binding Proteins/metabolism Regulatory Sequences, Ribonucleic Acid Uracil/analysis beta Catenin/metabolism
Chemicals
3' Untranslated Regions Antigens, Surface ELAV Proteins ELAV-Like Protein 1 ELAVL1 protein, human RNA, Messenger RNA-Binding Proteins Regulatory Sequences, Ribonucleic Acid beta Catenin Uracil Cyclooxygenase 2 Adenine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lee Hee Kyu
Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Republic of Korea.
Jeong Sunjoo
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkl698
Published
2006-00-00
Epub
2006-00-12
Pages
5705-14
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1636482
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkl698 PMC Full Text View journal details
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