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

Authors :
Ward, Jennifer A.
McLellan, Lauren
Stockley, Martin
Gibson, Karl R.
Whitlock, Gavin A.
Knights, Charlotte
Harrigan, Jeanine A.
Jacq, Xavier
Tate, Edward W.
Source :
ACS Chemical Biology; December 2016, Vol. 11 Issue: 12 p3268-3272, 5p
Publication Year :
2016

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 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.

Details

Language :
English
ISSN :
15548929 and 15548937
Volume :
11
Issue :
12
Database :
Supplemental Index
Journal :
ACS Chemical Biology
Publication Type :
Periodical
Accession number :
ejs40293176
Full Text :
https://doi.org/10.1021/acschembio.6b00766