IDENTIFYING TARGETS OF E3 UBIQUITIN LIGASES:ROLE IN BRCA1-MEDIATED BREAST CANCER

确定 E3 泛素连接酶的靶标：在 BRCA1 介导的乳腺癌中的作用

• 批准号: 7609721
• 负责人: David J Davido
• 金额: $ 2.09万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609721
• 关键词: Biochemical; Breast; Cancer Etiology; Cancer-Predisposing Gene; Cell Proliferation; Cellular biology; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Detection; Development; Diagnostic; Event; Funding; Genes; Goals; Grant; Institution; Malignant Neoplasms; Methods; Molecular; Mutation; Proteins; Research; Research Personnel; Resources; Role; Source; System; Techniques; Testing; Tumor Suppressor Proteins; United States; United States National Institutes of Health; Woman; base; innovation; malignant breast neoplasm; protein degradation; success; therapeutic target; tumor; tumorigenesis; ubiquitin-protein ligase

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Breast cancer is the second leading cause of cancers deaths in women in the United States. It is estimated that between 5-10% of breast cancers have a heritiable basis, and mutations in breast cancer susceptibility gene 1 (BRCA1) gene contribute significantly to the development of these cancers. BRCA1 is a tumor suppressor protein that inhibits the uncontrolled proliferation of cells, in part, by promoting the destruction of other cellular proteins as an E3 ubiquitin (Ub) ligase. Current methods for identifying targets of E3 Ub ligases have met with limited success. As a result, it is largely unclear which cellular proteins BRCA1 breaks down or degrades. The long-term goal of our research is to understand how protein degradation leads to cellular proliferation and tumor development. The objective of this proposal is to develop an innovative strategy to isolate targets of E3 Ub ligases (which includes BRCA1), relating the expression of BRCA1 targets to its anti-proliferative activity. To test this hypothesis, we will use a variety of virological, biochemical, and cell biology techniques to develop this system and identify BRCA1 targets. The primary rationale for these studies is to characterize the molecular events in the initiation of breast cancer. Results from our studies will be significant because the cellular proteins we will identify with our strategy can be used as potential diagnostic markers in the detection of and as therapeutic targets in breast tumorigenesis.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 乳腺癌是美国女性癌症死亡的第二大原因。 据估计，5-10% 的乳腺癌具有遗传基础，乳腺癌易感基因 1 (BRCA1) 基因的突变对这些癌症的发展有显着影响。 BRCA1 是一种肿瘤抑制蛋白，可部分通过促进 E3 泛素 (Ub) 连接酶等其他细胞蛋白的破坏来抑制细胞不受控制的增殖。 目前识别 E3 Ub 连接酶靶标的方法取得的成功有限。 因此，目前尚不清楚哪些细胞蛋白 BRCA1 会分解或降解。 我们研究的长期目标是了解蛋白质降解如何导致细胞增殖和肿瘤发展。 该提案的目的是开发一种创新策略来分离 E3 Ub 连接酶（包括 BRCA1）的靶标，将 BRCA1 靶标的表达与其抗增殖活性联系起来。 为了检验这一假设，我们将使用各种病毒学、生化和细胞生物学技术来开发该系统并识别 BRCA1 靶点。 这些研究的主要理由是描述乳腺癌发生过程中的分子事件。 我们的研究结果将具有重要意义，因为我们将通过我们的策略鉴定的细胞蛋白可用作乳腺肿瘤发生检测中的潜在诊断标记物和治疗靶标。