Biology of the P53 Protein

P53 蛋白的生物学

基本信息

批准号：
7483621
负责人：
RENATO Luigi BASERGA
金额：
$ 21.02万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-02-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7483621
关键词：
Abnormal Cell Agar Aging Animals Binding Biogenesis Biological Biology Body Size Caenorhabditis elegans Cancer Biology Cell Communication Cell Cycle Progression Cell Line Cell Nucleolus Cell Nucleus Cell Proliferation Cell Size Cell division Cells Cultured Cells DNA Polymerase I DNA-Directed RNA Polymerase Data Docking Drosophila genus Embryo Fibroblasts Genes Genetic Transcription Grant Growth Growth Factor Growth Factor Receptors Homologous Gene Human Industry Insulin-Like-Growth Factor I Receptor Knowledge Lead Light Link Literature Longevity Messenger RNA Molecular Mus Myeloid Cells Nuclear Nuclear Translocation Oncogenic Personal Satisfaction Phosphorylation Play Protein Binding Protein p53 Proteins Proto-Oncogenes RNA RNA Polymerase I RNA chemical synthesis Reagent Receptor Signaling Recombinant DNA Regulation Research Personnel Retinoblastoma Protein Ribosomal DNA Ribosomal RNA Ribosomes Role SV40 T Antigens Signal Transduction Somatomedins TP53 gene Tumor Suppressor Proteins Viral Oncogene Viral Tumor Antigens cell growth cell transformation in vivo insight insulin receptor substrate 1 protein metaplastic cell transformation neuronal cell body programs promoter protein activation research study sialosyl-T antigen size transcription factor UBF

项目摘要

DESCRIPTION (provided by applicant): The type 1 insulin-like growth factor receptor (IGF-IR) has recently become one of the favorite targets of industry 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 insulin 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.

描述（由申请人提供）：1型胰岛素样生长因子受体（IGF-IR）最近已成为行业最喜欢的目标之一，因为它在正常和异常细胞的生长中可能作用。从秀丽隐杆线虫到哺乳动物，IGF-IR信号传导在寿命中也起着重要作用。 IGF轴以非冗余的方式控制动物和培养细胞的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。 IRS-1（或其在果蝇中的同源物）的删除会导致大约50％的动物或细胞。我们最近发现，IRS-1易位到核结合并激活UBF1（上游结合因子1），该蛋白质可调节RNA聚合酶I活性，从而调节细胞（体内）大小。在此应用中，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核糖体DNA启动子激活的机制； 3）IRS-1与SV40 T抗原和选择的RNA聚合酶-2导向启动子N的物理和生物学相互作用，细胞的核，这种相互作用可能对细胞的转化至关重要。这些研究直接影响了我们对癌症生物学的基本知识，并可能阐明衰老的机制。