共查询到20条相似文献,搜索用时 15 毫秒
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Huang Z Xie H Ioannidis V Held W Clevers H Sadim MS Sun Z 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(8):4880-4887
By interacting with MHC class II molecules, CD4 facilitates lineage development as well as activation of Th cells. Expression of physiological levels of CD4 requires a proximal CD4 enhancer to stimulate basic CD4 promoter activity. T cell factor (TCF)-1/beta-catenin pathway has previously been shown to regulate thymocyte survival via up-regulating antiapoptotic molecule Bcl-xL. By both loss and gain of function studies, in this study we show additional function of TCF-1/beta-catenin pathway in the regulation of CD4 expression in vivo. Mice deficient in TCF-1 displayed significantly reduced protein and mRNA levels of CD4 in CD4+ CD8+ double-positive (DP) thymocytes. A transgene encoding Bcl-2 restored survival but not CD4 levels of TCF-1(-/-) DP cells. Thus, TCF-1-regulated survival and CD4 expression are two separate events. In contrast, CD4 levels were restored on DP TCF-1(-/-) cells by transgenic expression of a wild-type TCF-1, but not a truncated TCF-1 that lacks a domain required for interacting with beta-catenin. Furthermore, forced expression of a stabilized beta-catenin, a coactivator of TCF-1, resulted in up-regulation of CD4. TCF-1 or stabilized beta-catenin greatly stimulated activity of a CD4 reporter gene driven by a basic CD4 promoter and the CD4 enhancer. However, mutation of a potential TCF binding site located within the enhancer abrogated TCF-1 and beta-catenin-mediated activation of CD4 reporter. Finally, recruitment of TCF-1 to CD4 enhancer was detected in wild-type but not TCF-1 null mice by chromatin-immunoprecipitation analysis. Thus, our results demonstrated that TCF/beta-catenin pathway enhances CD4 expression in vivo by recruiting TCF-1 to stimulate CD4 enhancer activity. 相似文献
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Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling 总被引:1,自引:0,他引:1
Yasumoto K Takeda K Saito H Watanabe K Takahashi K Shibahara S 《The EMBO journal》2002,21(11):2703-2714
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Koh SS Li H Lee YH Widelitz RB Chuong CM Stallcup MR 《The Journal of biological chemistry》2002,277(29):26031-26035
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Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets 总被引:11,自引:0,他引:11
Park JI Kim SW Lyons JP Ji H Nguyen TT Cho K Barton MC Deroo T Vleminckx K Moon RT McCrea PD 《Developmental cell》2005,8(6):843-854
Beta-catenin-dependent or canonical Wnt signals are fundamental in animal development and tumor progression. Using Xenopus laevis, we report that the BTB/POZ zinc finger family member Kaiso directly represses canonical Wnt gene targets (Siamois, c-Fos, Cyclin-D1, and c-Myc) in conjunction with TCF/LEF (TCF). Analogous to beta-catenin relief of TCF repressive activity, we show that p120-catenin relieves Kaiso-mediated repression of Siamois. Furthermore, Kaiso and TCF coassociate, and combined Kaiso and TCF derepression results in pronounced Siamois expression and increased beta-catenin coprecipitation with the Siamois promoter. The functional interdependency is underlined by Kaiso suppression of beta-catenin-induced axis duplication and by TCF-3 rescue of Kaiso depletion phenotypes. These studies point to convergence of parallel p120-catenin/Kaiso and beta-catenin/TCF signaling pathways to regulate gene expression in vertebrate development and possibly carcinogenesis. 相似文献
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The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells 总被引:56,自引:0,他引:56
van de Wetering M Sancho E Verweij C de Lau W Oving I Hurlstone A van der Horn K Batlle E Coudreuse D Haramis AP Tjon-Pon-Fong M Moerer P van den Born M Soete G Pals S Eilers M Medema R Clevers H 《Cell》2002,111(2):241-250
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