Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells
详细信息 查看全文
- 作者：Jennifer A. Ward ; Lauren McLellan ; Martin Stockley ; Karl R. Gibson ; Gavin A. Whitlock ; Charlotte Knights ; Jeanine A. Harrigan ; Xavier Jacq ; Edward W. Tate
- 刊名：ACS Chemical Biology
- 出版年：2016
- 出版时间：December 16, 2016
- 年：2016
- 卷：11
- 期：12
- 页码：3268-3272
- 全文大小：365K
- ISSN：1554-8937
文摘
Deubiquitinating enzymes play an important role in a plethora of therapeutically relevant processes and are emerging as pioneering drug targets. Herein, we present a novel probe, Ubiquitin Specific Protease (USP) inhibitor, alongside an alkyne-tagged activity-based probe analogue. Activity-based proteome profiling identified 12 USPs, including USP4, USP16, and USP33, as inhibitor targets using submicromolar probe concentrations. This represents the first intact cell activity-based profiling of deubiquitinating enzymes. Further analysis demonstrated functional inhibition of USP33 and identified a synergistic relationship in combination with ATR inhibition, consistent with USP4 inhibition.