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

项目摘要 细胞的恶性转化推动了肿瘤的发展。癌细胞可以是 今天例行的基因分型显示了大量的体细胞突变。然而，它仍然 不清楚哪些突变会导致恶性转化并提供生存 对癌细胞有利，而这些只是乘客突变。而不是解剖 每一种突变都是通过克隆和超表达等生化技术单独进行的，我们 建议系统地描绘癌细胞蛋白质组以寻找蛋白质表面改变 可获得性，这有助于更好地理解体细胞突变对蛋白质组的影响 功能和活动。揭示了蛋白质表面可及性中的新纯摄动 一种新的、定量的体内化学标记方法与枪炮蛋白质组学相结合。这个 新的方法可以作为一种平台技术来筛选患者来源的癌细胞和 有希望在蛋白质组中精确定位关键的、癌细胞特有的扰动。

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.