WNT TARGET GENE REGULATION BY BETA-CATENIN AND THE APC TUMOR SUPPRESSOR

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 LEF-1/TCF DNA结合蛋白介导Wnt/Wg信号传导事件，其调节肠上皮祖细胞和干细胞的细胞增殖、器官形成和自我更新。 Wnt通路的异常调节在许多癌症中起关键作用。 例如，近85%的人结直肠癌含有肿瘤抑制剂腺瘤性息肉病结肠蛋白（APC）的突变，该蛋白控制LEF-1转录共激活因子β-连环蛋白的稳定性和核积累。 我们的目标是表征APC肿瘤抑制因子对β-连环蛋白：LEF-1激活和转录抑制的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The LEF-1/TCF DNA-binding proteins mediate Wnt/Wg signaling events that regulate cell proliferation, organogenesis, and self-renewal of intestinal epithelial progenitor and stem cells. Aberrant regulation of the Wnt pathway plays a key role in many cancers. For example, nearly 85% of human colorectal cancers contain mutations in the tumor suppressor adenomatous polyposis coli protein (APC), which controls the stability and nuclear accumulation of the LEF-1 transcriptional co-activator, beta-catenin. Our goal is to characterize the mechanism of beta-catenin:LEF-1 activation and transcriptional repression by the APC tumor suppressor.