Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3'-UTR.
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.
Lee
Hee Kyu
HK
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
S
D020413:3' Untranslated Regions / Q000737:chemistry* / Q000378:metabolism; D000225:Adenine / Q000032:analysis; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D014498:Uracil / Q000032:analysis; D051176:beta Catenin / Q000378:metabolism*
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D051176:beta Catenin; D014498:Uracil; D051546:Cyclooxygenase 2; D000225:Adenine