BIOLOGY OF THE P53 PROTEIN

P53 蛋白的生物学

• 批准号: 6849319
• 负责人: RENATO Luigi BASERGA
• 金额: $ 22.66万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2006-09-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849319
• 关键词: BIOLOGY; P53; PROTEIN

EXCEED THE SPACE PROVIDED. The type 1 insulin-like growth factor receptor (IGF-IR) has recently become one of the favorite targets of ndustry for its possible role in the growth of normal and abnormal cells. IGF-IR signaling also plays a significant role in longevity, from C. elegans to mammalians. The IGF axis controls, in a non-redundant way, about 50% of growth in animals and cells in culture, largely through the activation of its docking protein, the nsulin receptor substrate-1 (IRS-1). Deletion of IRS-1 (or its homologues in Drosophila) results in animals or cells that are roughly 50% in size. We have recently found that IRS-1 translocates to the nuclei where it binds and activates UBF1 (Upstream Binding Factor 1), a protein that regulates RNA polymerase I activity, and therefore cell (and body) size. In this application, we propose to study: 1) the mechanism by which IRS-1 regulates the activity and/or the stability of UBF1; 2) the mechanism(s) by which nuclear IRS-1 competes with other nucleolar proteins for the activation of the ribosomal DNA promoter; and 3) the physical and biological interactions of IRS-1 with the SV40 T antigen and selected RNA polymerase-2-directed promoters n the nuclei of cells, an interaction that may be critical for the transformation of cells. These studies have a direct impact on our basic knowledge of the biology of cancer and may throw light on mechanisms of aging. PERFORMANCE SITE ========================================Section End===========================================

超出提供的空间。I型胰岛素样生长因子受体(IGF-IR)因其在正常和异常细胞生长中的可能作用而成为近年来研究的热点之一。IGF-IR信号在从线虫到哺乳动物的长寿过程中也发挥着重要作用。IGF轴以一种非冗余的方式控制着动物和培养细胞中约50%的生长，主要是通过激活其对接蛋白-胰岛素受体底物-1(IRS-1)。IRS-1(或其在果蝇中的同源物)的缺失会导致动物或细胞的大小约为50%。我们最近发现IRS-1易位到细胞核，在那里它结合并激活UBF1(上游结合因子1)，UBF1(上游结合因子1)是一种调节RNA聚合酶I活性的蛋白质，因此调节细胞(和身体)的大小。在这一应用中，我们建议研究：1)IRS-1调节UBF1活性和/或稳定性的机制；2)核IRS-1与其他核仁蛋白竞争激活核糖体DNA启动子的机制(S)；以及3)IRS-1与SV40T抗原和选定的RNA聚合酶-2在细胞核中的启动子的物理和生物相互作用，这种相互作用可能是细胞转化的关键。这些研究直接影响到我们对癌症生物学的基本知识，并可能有助于揭示衰老的机制。表演网站========================================Section End===========================================