Quantitative Proteomics of the Cancer Cell Line Encyclopedia
Quantitative Proteomics of the Cancer Cell Line Encyclopedia
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DOI：
10.1016/j.cell.2019.12.023
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发表时间：
2020-01-23
期刊：
影响因子：
64.5
通讯作者：
Gygil, Steven P.
中科院分区：
文献类型：
--
作者：
Nusinow, David P.;Szpyt, John;Gygil, Steven P.
蛋白质是生物过程中必不可少的物质。迄今为止，包括癌细胞系百科全书（CCLE）在内的细胞系集合的大规模分析主要集中在遗传信息上，而蛋白质组的深入研究仍然遥不可及。在这里，我们通过质谱法对来自不同谱系的375个细胞系的数千种蛋白质进行定量分析，以揭示DNA和RNA方法未发现的信息，从而扩展了CCLE。我们观察到RNA中基本上不存在的通路内部和之间的意外相关性。对微卫星不稳定（MSI）细胞系的分析揭示了与突变和翻译监视相关的特定蛋白质复合物的失调。这些和其他蛋白质复合物与对几种不同基因敲除的敏感性相关。这些数据与更广泛的CCLE相结合，是探索细胞行为和促进癌症研究的广泛资源。
Proteins are essential agents of biological processes. To date, large-scale profiling of cell line collections including the Cancer Cell Line Encyclopedia (CCLE) has focused primarily on genetic information whereas deep interrogation of the proteome has remained out of reach. Here, we expand the CCLE through quantitative profiling of thousands of proteins by mass spectrometry across 375 cell lines from diverse lineages to reveal information undiscovered by DNA and RNA methods. We observe unexpected correlations within and between pathways that are largely absent from RNA. An analysis of microsatellite instable (MSI) cell lines reveals the dysregulation of specific protein complexes associated with surveillance of mutation and translation. These and other protein complexes were associated with sensitivity to knockdown of several different genes. These data in conjunction with the wider CCLE are a broad resource to explore cellular behavior and facilitate cancer research.