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

项目摘要 细胞的恶性转化驱动肿瘤的发展。癌细胞可以 如今常规的基因分型揭示了大量的体细胞突变。但委员会仍 不清楚哪些突变导致恶性转化并提供生存 这些突变对癌细胞有利，并且只是乘客突变。而不是解剖 通过生物化学技术如克隆和过表达， 我建议系统地分析癌细胞蛋白质组，以改变蛋白质表面 可访问性，这可以帮助更好地了解体细胞突变对蛋白质组的影响 功能和活动。蛋白质表面可及性的新形态扰动被揭示为 一个新的，定量的，在体内的化学标记方法耦合到猎枪蛋白质组学。的 新方法可用作筛选患者来源的癌细胞的平台技术， 有望精确定位蛋白质组中关键的癌细胞特异性扰动。

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.