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

ABSTRACT: 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 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 nanomolar 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Osteosarcoma Cell Line

SUBMITTER: Jenny Ward  

LAB HEAD: Edward W Tate

PROVIDER: PXD004875 | Pride | 2016-12-14

REPOSITORIES: Pride