Biology of the P53 Protein
P53 蛋白的生物学
基本信息
- 批准号:7284862
- 负责人:
- 金额:$ 21.02万
- 依托单位:
- 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:
- 关键词:Abnormal CellAgarAgingAnimalsBindingBiogenesisBiologicalBiologyBody SizeCaenorhabditis elegansCancer BiologyCell CommunicationCell Cycle ProgressionCell LineCell NucleolusCell NucleusCell ProliferationCell SizeCell divisionCellsCultured CellsDNA Polymerase IDNA-Directed RNA PolymeraseDataDockingDrosophila genusEmbryoFibroblastsGenesGenetic TranscriptionGrantGrowthGrowth FactorGrowth Factor ReceptorsHomologous GeneHumanIndustryInsulin-Like-Growth Factor I ReceptorKnowledgeLeadLightLinkLiteratureLongevityMessenger RNAMolecularMusMyeloid CellsNuclearNuclear TranslocationOncogenicPersonal SatisfactionPhosphorylationPlayProtein BindingProtein p53ProteinsProto-OncogenesRNARNA Polymerase IRNA chemical synthesisReagentReceptor SignalingRecombinant DNARegulationResearch PersonnelRetinoblastoma ProteinRibosomal DNARibosomal RNARibosomesRoleSV40 T AntigensSignal TransductionSomatomedinsTP53 geneTumor Suppressor ProteinsViral OncogeneViral Tumor Antigenscell growthcell transformationin vivoinsightinsulin receptor substrate 1 proteinmetaplastic cell transformationneuronal cell bodyprogramspromoterprotein activationresearch studysialosyl-T antigensizetranscription 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(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RENATO Luigi BASERGA其他文献
RENATO Luigi BASERGA的其他文献
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