Structure, dynamics and function of RNA binding proteins

RNA结合蛋白的结构、动力学和功能

基本信息

批准号：
8330764
负责人：
Francesca Massi
金额：
$ 31.26万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8330764
关键词：
Accounting Affinity Amino Acids Apoptosis Binding Binding Proteins Binding Sites Biochemical Biological Process Breast Cell Proliferation Cells Cessation of life Chimeric Proteins Chronic Computer Simulation Coupled Data Discrimination Disease Family Family member Fluorescence Spectroscopy Functional disorder Future Gene Expression Regulation Genetic Transcription Glioma Goals Growth Factor Human Individual Inflammation Laboratories Lead Ligands Link Malignant Neoplasms Mammalian Cell Measures Mediating Messenger RNA Molecular NMR Spectroscopy Phenotype Phosphorylation Physiologic pulse Play Process Production Prostate Protein Binding Protein Family Proteins RNA RNA Binding RNA Recognition Motif RNA-Binding Proteins Radioactive Recruitment Activity Regulation Resistance Role Serine Site-Directed Mutagenesis Specificity Staging Structure TIS11 protein Techniques Testing United States Vascularization Work Zinc Fingers angiogenesis base cancer type conformational conversion cytokine flexibility improved in vivo innovation interdisciplinary approach mRNA Decay mRNA Transcript Degradation member molecular dynamics novel therapeutic intervention protein function research study tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): Regulation of gene expression is central to efficient biological function. Two key aspects of this process are the synthesis of mRNA (transcription) and control of its stability. The goal of this proposal is to understand how an important class of proteins, the CCCH zinc finger proteins of the tristetraprolin (TTP) family, recognizes and binds to mRNA to promote its degradation. This process provides an important mechanism for reducing the synthesis of key cytokines and growth factors that regulate inflammation and the initiation and progression of cancer. To understand the function and regulation of TTP in the cell we will use an integrated approach that combines NMR spectroscopy, computer simulation, biochemical and in vivo experiments. Our detailed biophysical and biochemical characterizations of TTP-mRNA interactions will determine the mechanism of TTP-mediated mRNA destabilization that is relevant for cancer and inflammation.

描述（由申请人提供）：基因表达的调节对于有效的生物学功能至关重要。该过程的两个关键方面是mRNA（转录）及其稳定性的控制。该提案的目的是了解重要类别的蛋白质，即三角烷酸蛋白（TTP）家族的CCCH锌指蛋白如何识别并结合mRNA以促进其降解。该过程提供了减少调节炎症以及癌症开始和进展的关键细胞因子和生长因子的合成的重要机制。为了了解细胞中TTP的功能和调节，我们将使用结合NMR光谱，计算机模拟，生化和体内实验的集成方法。我们对TTP-MRNA相互作用的详细生物物理和生化特征将确定与癌症和炎症有关的TTP介导的mRNA不稳定的机制。