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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 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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Ward JA,McLellan L,Stockley M,Gibson KR,Whitlock GA,Knights C,Harrigan JA,Jacq X,Tate EW

doi

10.1021/acschembio.6b00766

subject

Has Abstract

pub_date

2016-12-16 00:00:00

pages

3268-3272

issue

12

eissn

1554-8929

issn

1554-8937

journal_volume

11

pub_type

信件

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