Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells.

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.
Mesh Terms:
Alkynes, Cell Line, Tumor, Humans, Molecular Probe Techniques, Molecular Probes, Neoplasms, Proteomics, Pyrroles, Small Molecule Libraries, Ubiquitin-Specific Proteases
ACS Chem Biol
Date: Dec. 16, 2015
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