共查询到20条相似文献,搜索用时 31 毫秒
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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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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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Willinger T Freeman T Herbert M Hasegawa H McMichael AJ Callan MF 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(3):1439-1446
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