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

β-连环蛋白和 APC 肿瘤抑制因子对 WNT 靶基因的调控

• 批准号: 8365827
• 负责人: KATHERINE A JONES
• 金额: $ 1.28万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365827
• 关键词: Adenomatous Polyposis Coli Protein; Biology; Cell Proliferation; Colorectal Cancer; DNA-Binding Proteins; Epithelial; Event; Funding; Fungal Genome; Gene Expression Regulation; Goals; Grant; Human; Intestines; Malignant Neoplasms; Mediating; Mutation; National Center for Research Resources; Nuclear; Organogenesis; Pathway interactions; Play; Principal Investigator; Regulation; Research; Research Infrastructure; Resources; Signal Transduction; Source; Stem cells; Tumor Suppressor Proteins; United States National Institutes of Health; beta catenin; cost; gene repression; progenitor; self-renewal

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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 Lef-1/TCFDNA结合蛋白介导Wnt/Wg信号事件，调节细胞增殖、器官发生和肠上皮祖细胞和干细胞的自我更新。Wnt通路的异常调节在许多癌症中起着关键作用。例如，近85%的人类结直肠癌含有肿瘤抑制因子腺瘤性息肉病结肠蛋白(APC)的突变，APC控制着Lef-1转录辅助激活因子β-catenin的稳定性和核积累。我们的目标是描述β-连环蛋白的机制：Lef-1激活和APC肿瘤抑制因子的转录抑制。