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===========================================

超出所提供的空间。1型胰岛素样生长因子受体（IGF-IR）因其在正常和异常细胞的生长中可能发挥的作用而成为近年来工业界最喜欢的靶点之一。从秀丽隐杆线虫到哺乳动物，IGF-IR信号在长寿中也起着重要作用。IGF轴以一种非冗余的方式控制动物和培养细胞中约50%的生长，主要是通过其对接蛋白胰岛素受体底物-1 （IRS-1）的激活。删除IRS-1（或果蝇的同源物）会导致动物或细胞的大小缩小大约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。在这个应用中，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；3) IRS-1与SV40 T抗原和细胞核中选定的RNA聚合酶2导向启动子的物理和生物相互作用，这种相互作用可能对细胞转化至关重要。这些研究对我们对癌症生物学的基本知识有直接的影响，并可能阐明衰老的机制。网站性能 ======================================== 节结束 ===========================================