RNA结合蛋白的结构、动力学和功能-猫眼课题宝

RNA结合蛋白的结构、动力学和功能

批准号：

8727062

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

项目状态：

已结题

起止时间：

2011-09-15 至 2016-08-31

来源：

https://reporter.nih.gov/project-details/8727062

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 biophysical techniques 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

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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.

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