| First Author | Yun K | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 364 |
| Issue | 2 | Pages | 270-5 |
| PubMed ID | 17945188 | Mgi Jnum | J:127429 |
| Mgi Id | MGI:3763752 | Doi | 10.1016/j.bbrc.2007.09.129 |
| Citation | Yun K, et al. (2007) Lef1 regulates COX-2 transcription in chondrocytes. Biochem Biophys Res Commun 364(2):270-5 |
| abstractText | Although the involvement of Wnt/beta-catenin signaling pathway in the regulation of COX-2 expression has been suggested, the underlying molecular mechanisms are still unclear. Here, we demonstrate that lymphoid enhancer-binding factor 1 (Lef1) in concert with beta-catenin is associated with the transcriptional regulation of the gene encoding COX-2 in mouse chondrocytes. Our results show that co-overexpression of Lef1 and beta-catenin synergistically upregulates COX-2 expression. Furthermore, decrease of Lef1 expression using Lef1 siRNA results in the downregulation of COX-2 expression. Using bioinformatic analysis, we identified a conserved Lef1-binding site that is mapped at the 3' region of the genomic COX-2 locus. In vivo and in vitro binding of Lef1 at the predicted binding site was proved using chromatin immunoprecipitation assays and electrophoretic mobility shift assays, respectively. Moreover, binding of Lef1 and beta-catenin to the Lef1-binding site transactivates COX-2 promoter activity. Our results indicate a pivotal role of Lef1 in the regulation of COX-2 transcription in arthritic chondrocytes. |
