B-Catenin regulation by the Proto-Oncoprotein SYT

原癌蛋白 SYT 对 B-连环蛋白的调节

• 批准号: 6757538
• 负责人: JOSIANE E EID
• 金额: $ 23.78万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6757538
• 关键词: RNA interference; bone neoplasms; cadherins; cell line; chromatin immunoprecipitation; confocal scanning microscopy; gel mobility shift assay; genetic regulation; joints; laboratory mouse; neoplasm /cancer genetics; neoplastic transformation; oncoproteins; polymerase chain reaction; protein binding; protein localization; protein protein interaction; protein structure function; protooncogene; sarcoma; synovial membrane

DESCRIPTION (provided by applicant): Synovial sarcoma is a soft tissue tumor of the joints that affects young adults. It is characterized by a chromosomal translocation t(X; 18;pl 1;ql 1) that juxtaposes the SYT gene on chromosome 18 and the SSX gene on the X chromosome, resulting in the fusion, SYT-SSX. In the cancer, SYT-SSX is thought to exert a dominant gain of function, while the wt SYT allele is significantly down regulated, leading to loss of SYT normal function. a-catenin is the mediator of the wnt pathway, an active program in development and cancer. We found that SYT associates with beta-catenin in the nucleus and appears to suppress its function, while SYT-SSX activates it. The objective of this proposal is to characterize the functional relationship between SYT and beta-catenin, and its deregulation by SYT-SSX, in adult tissue and development. In addition, we will identify the nuclear components involved in this process and their role in mediating SYT and SYT-SSX effects on a-catenin. The aim of this research proposal is to help gain a clearer understanding of synovial sarcoma development.

描述（由申请人提供）：滑膜肉瘤是一种影响年轻人的关节软组织肿瘤。 其特征是染色体易位t(X; 18;pl 1;ql 1)，将18号染色体上的SYT基因与X染色体上的SSX基因并列，导致融合，SYT-SSX。 在癌症中，SYT-SSX 被认为具有显着的功能增益，而 wt SYT 等位基因显着下调，导致 SYT 正常功能丧失。 a-连环蛋白是 WNT 通路的调节者，WNT 通路是发育和癌症中的一个活跃程序。 我们发现 SYT 与细胞核中的 β-连环蛋白结合并似乎抑制其功能，而 SYT-SSX 则激活它。该提案的目的是表征 SYT 和 β-catenin 之间的功能关系，以及 SYT-SSX 在成人组织和发育中对其的解除调节。 此外，我们将确定参与该过程的核成分及其在介导 SYT 和 SYT-SSX 对 a-catenin 影响中的作用。本研究计划的目的是帮助更清楚地了解滑膜肉瘤的发展。