ACS Chem Biol. 2022 Apr 15;17(4):776-784. doi: 10.1021/acschembio.2c00018. Epub 2022 Mar 21.
To aid in the prioritization of deubiquitinases (DUBs) as anticancer targets, we developed an approach combining activity-based protein profiling (ABPP) with mass spectrometry in both non-small cell lung cancer (NSCLC) tumor tissues and cell lines along with analysis of available RNA interference and CRISPR screens. We identified 67 DUBs in NSCLC tissues, 17 of which were overexpressed in adenocarcinoma or squamous cell histologies and 12 of which scored as affecting lung cancer cell viability in RNAi or CRISPR screens. We used the CSN5 inhibitor, which targets COPS5/CSN5, as a tool to understand the biological significance of one of these 12 DUBs, COPS6, in lung cancer. Our study provides a powerful resource to interrogate the role of DUB signaling biology and nominates druggable targets for the treatment of lung cancer subtypes.
为了帮助确定去泛素化酶（DUBs）作为抗癌靶点的优先级，我们开发了一种结合活性蛋白质谱分析（ABPP）和质谱分析的方法，分别在非小细胞肺癌（NSCLC）肿瘤组织和细胞系中进行，同时还分析了现有的 RNA 干扰和 CRISPR 筛选结果。我们在 NSCLC 组织中鉴定出 67 种 DUBs，其中 17 种在腺癌或鳞状细胞组织学中过度表达，12 种在 RNAi 或 CRISPR 筛选中影响肺癌细胞活力。我们使用 CSN5 抑制剂（靶向 COPS5/CSN5）作为工具，研究其中一种 DUB，即 COPS6，在肺癌中的生物学意义。我们的研究为研究 DUB 信号生物学的作用提供了有力的资源，并为治疗肺癌亚型提名了可成药的靶点。
