Measurement of Aberrant Protein Folds in Malignant Cells with Proteomics and Mass Spectrometry

用蛋白质组学和质谱法测量恶性肿瘤细胞中的异常蛋白质折叠

基本信息

批准号：
9233438
负责人：
John R Yates III
金额：
$ 43.56万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-10 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9233438
关键词：
1-Phosphatidylinositol 3-Kinase Amination Amines Architecture Biochemical Bioinformatics Biopsy Breast Epithelial Cells Cell Line Cells Charge Chemicals Cloning Computer Simulation Coupled Crystallization DNA DNA Binding DNA Binding Domain DNA Sequence Alteration Detection Development Digestion Environment Evolution Genotype Guns Individual Isotopes K-ras Oncogene Label Lysine MCF10A cells Malignant - descriptor Malignant Neoplasms Mass Spectrum Analysis Measurement Measures Membrane Proteins Methods Methylation Modification Molecular Mus Mutate Mutation Non-Malignant PIK3CA gene Patients Peptides Point Mutation Protein p53 Proteins Proteome Proteomics Proto-Oncogenes RNA Reaction Reagent Reproducibility Research Sampling Screening for cancer Solvents Somatic Cell Somatic Mutation Structure Surface Techniques Technology Temperature Testing Therapeutic Intervention Time Validation amino group base biological adaptation to stress cancer cell cell transformation chemical reaction experimental study in vivo insight misfolded protein mouse model new technology novel novel strategies overexpression protein folding protein misfolding protein structure response stable isotope targeted cancer therapy targeted treatment tool tumor

项目摘要

Project Summary Malignant transformation of cells drives the development of tumors. Cancer cells can be routinely genotyped today revealing a large number of somatic mutations. However, it remains unclear which mutations contribute to malignant transformation and provide a survival advantage to cancer cells and which are simply passenger mutations. Rather than dissecting each mutation individually by biochemical techniques such as cloning and overexpression, we propose to systematically profile the proteome of cancer cells for altered protein surface accessibility, which can help to better understand the impact of somatic mutations on proteome function and activity. Neomorphic perturbations in protein surface accessibility is revealed with a new, quantitative, in vivo chemical labeling approach coupled to shot gun proteomics. The novel approach can be used as a platform technology to screen patient-derived cancer cells and holds promise to pinpoint critical, cancer cell specific perturbations in the proteome.

项目摘要细胞的恶性转化驱动肿瘤的发展。癌细胞可以是如今，常规的基因分型揭示了大量的体细胞突变。但是，它仍然是不清楚哪些突变导致恶性转化并提供生存对癌细胞的优势，仅仅是乘客突变。而不是解剖每个突变通过生化技术（例如克隆和过表达）单独进行，我们提议系统地介绍癌细胞的蛋白质组改变蛋白质表面可访问性，这可以帮助更好地理解躯体突变对蛋白质组的影响功能和活动。蛋白质表面可及性中的新态扰动显示一种新的，定量的体内化学标记方法，结合了射击枪支蛋白质组学。这新方法可以用作筛查患者衍生的癌细胞的平台技术和有望确定蛋白质组中关键的癌细胞特异性扰动。