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Logo of bmcchbBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Chemical Biology
BMC Chem Biol. 2012; 12: 4.
Published online May 14, 2012. doi:  10.1186/1472-6769-12-4
PMCID: PMC3475094
Identification Of Small Molecule TRABID Deubiquitinase Inhibitors By Computation-Based Virtual Screen
Tong Shi,#1 Ju Bao,#2 Nick X Wang,#2 Jie Zheng,corresponding author2 and Dianqing Wucorresponding author1
1Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA
2Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
corresponding authorCorresponding author.
#Contributed equally.
Tong Shi: Tong.shi/at/; Ju Bao: Ju.bao/at/; Nick X Wang:; Jie Zheng: jie.zheng/at/; Dianqing Wu: Dan.wu/at/
Received October 5, 2011; Accepted April 19, 2012.
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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