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Biology of the P53 Protein

P53 蛋白的生物学

基本信息

批准号：
7668032
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/7668032
关键词：
Abnormal Cell Agar Age Animals Binding Biogenesis Biological Biology Body Size Caenorhabditis elegans Cancer Biology Cell Communication Cell Culture Techniques Cell Cycle Progression Cell Line Cell Nucleolus Cell Nucleus Cell Proliferation Cell Size Cell division 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 Nucleolar Proteins Oncogenic 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 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 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（申请人提供）：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，近年来成为工业界最喜欢的靶标之一。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着动物和培养细胞中约50%的生长，主要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。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Subcellular localization of IRS-1 in cell proliferation and differentiation.

IRS-1 在细胞增殖和分化中的亚细胞定位。

DOI：
10.1055/s-2004-814155
发表时间：
2003
期刊：
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
影响因子：
0
作者：
Tu,X;Wu,A;Maiorana,A;Baserga,R
通讯作者：
Baserga,R

Nuclear translocation of insulin receptor substrate-1 by the insulin receptor in mouse embryo fibroblasts.

小鼠胚胎成纤维细胞中胰岛素受体对胰岛素受体底物 1 的核易位。

DOI：
10.1002/jcp.10261
发表时间：
2003
期刊：
Journal of cellular physiology.
影响因子：
0
作者：
Wu,An;Sciacca,Laura;Baserga,Renato
通讯作者：
Baserga,Renato

Deletion of the pleckstrin and phosphotyrosine binding domains of insulin receptor substrate-2 does not impair its ability to regulate cell proliferation in myeloid cells.

DOI：
10.1210/en.2004-0668
发表时间：
2004-11
期刊：
Endocrinology
影响因子：
4.8
作者：
Hongzhi Sun;R. Baserga
通讯作者：
Hongzhi Sun;R. Baserga

Nuclear translocation of insulin receptor substrate-1 by oncogenes and Igf-I. Effect on ribosomal RNA synthesis.

癌基因和 Igf-I 导致胰岛素受体底物 1 发生核易位。

DOI：
10.1074/jbc.m208001200
发表时间：
2002
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Tu,Xiao;Batta,Priti;Innocent,Nathalie;Prisco,Marco;Casaburi,Ivan;Belletti,Barbara;Baserga,Renato
通讯作者：
Baserga,Renato

The role of insulin receptor substrate-1 in the oncogenicity of simian virus 40 T antigen.

胰岛素受体底物-1 在猿猴病毒 40 T 抗原致癌性中的作用。