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

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Title: Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells
Authors: Ward, JA
McLellan, L
Stockley, M
Gibson, KR
Whitlock, GA
Knights, C
Harrigan, JA
Jacq, X
Tate, EW
Item Type: Journal Article
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.
Issue Date: 25-Oct-2016
Date of Acceptance: 25-Oct-2016
URI: http://hdl.handle.net/10044/1/43848
DOI: https://dx.doi.org/10.1021/acschembio.6b00766
ISSN: 1554-8937
Publisher: American Chemical Society
Start Page: 3268
End Page: 3272
Journal / Book Title: ACS Chemical Biology
Volume: 11
Issue: 12
Copyright Statement: © 2016 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
DEUBIQUITYLATING ENZYMES
ACTIVE-SITE
PROBE
INHIBITION
ATM
DEUBIQUITINATION
HIF-1-ALPHA
EXPRESSION
REACTIVITY
PATHWAYS
Organic Chemistry
03 Chemical Sciences
06 Biological Sciences
Publication Status: Published
Appears in Collections:Chemistry
Biological and Biophysical Chemistry



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