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: 7234362
• 负责人: JOSIANE E EID
• 金额: $ 23.48万
• 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 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7234362
• 关键词: Adult; Affect; Alleles; Apoptosis; Cell Nucleus; Chimera organism; Chimeric Proteins; Chromatin; Chromosomal translocation; Chromosomes, Human, Pair 18; Complex; Development; Genes; Genetic Transcription; Joints; Lead; Light; Malignant Neoplasms; Mediating; Mediator of activation protein; Normal Cell; Nuclear; Oncogene Proteins; Oncogenes; Pathway interactions; Process; Protein translocation; Regulation; Research Proposals; Role; SMARCA4 gene; Signal Transduction; Soft Tissue Neoplasms; Solid Neoplasm; Thinking; Tissues; X Chromosome; beta catenin; carcinogenesis; cell growth; gain of function; intestinal epithelium; leukemia; neoplastic cell; programs; sarcoma; synovial sarcoma; tumor; tumorigenesis; young adult

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）：滑膜肉瘤是影响年轻人的关节的软组织肿瘤。 它的特征在于染色体易位T（x; 18; PL 1; QL 1），该染色体18染色体上的SYT基因和X染色体上的SSX基因并置，导致融合，SYT-SSX。 在癌症中，SYT-SSX被认为具有主要功能增益，而WT Syt等位基因被显着下调，从而导致SYT正常功能丧失。 A-Catenin是Wnt Pathway的中介，这是一个积极的发育和癌症计划。 我们发现SYT与核中的β-catenin相关联，似乎可以抑制其功能，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，及其在成人组织和发育中对SYT-SSX的放松管制。 此外，我们将确定该过程中涉及的核成分及其在介导SYT和SYT-SSX对A-catenin的影响中的作用。这项研究建议的目的是帮助对滑膜肉瘤的开发有更清晰的了解。