Quantitative Chemical Proteomic Profiling of Ubiquitin Specific Proteases in Intact Cancer Cells
File(s)
Published version
Author(s)
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.
Date Issued
2016-10-25
Date Acceptance
2016-10-25
Citation
ACS Chemical Biology, 2016, 11 (12), pp.3268-3272
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.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000390179700006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
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