Identification Of Small Molecule TRABID Deubiquitinase Inhibitors By Computation-Based Virtual Screen.

BMC Chemical Biology
Tong ShiDianqing Wu

Abstract

Wnt/β-catenin-mediated gene transcription plays important roles in a wide range of biological and pathophysiological processes including tumorigenesis where β-catenin-mediated transcription activity frequently elevates. TRABID, a deubiquitinase, was shown to have a positive Wnt/β-catenin-mediated gene transcription and hence holds a promise as a putative anti-cancer target. In this study, we used a combination of structure based virtual screening and an in vitro deubiquitinase (DUB) assay to identify several small molecules that inhibit TRABID DUB activity. However, these inhibitors failed to show inhibitory effects on β-catenin-mediated gene transcription. In addition, expression of TRABID shRNAs, wildtype TRABID, or the DUB activity-deficient mutant showed little effects on β-catenin-mediated gene transcription. TRABID may not be a critical component in canonical Wnt/β-catenin signal transduction or that a minute amount of this protein is sufficient for its role in regulating Wnt activity.

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Citations

Dec 3, 2014·Pharmacology & Therapeutics·Padraig D'ArcyStig Linder
Feb 18, 2016·Nature Immunology·Inna S Afonina, Rudi Beyaert
Aug 13, 2020·International Journal of Molecular Sciences·Jinhong ChoEun Joo Song
Jan 1, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
Jan 12, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
Apr 16, 2021·The Journal of Biological Chemistry·Lee D HarrisJulien D F Licchesi
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Nov 5, 2019·Journal of Medicinal Chemistry·Nathan J SchauerSara J Buhrlage
Aug 30, 2021·Biomarker Research·Hu LeiYingli Wu

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Methods Mentioned

BETA
deubiquitination
ubiquitination
transfection
PCR
Flow Cytometry

Software Mentioned

ICM PocketFinder
Schrodinger
AMBER10

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