Research article

BMC Chemical Biology

, 12:4

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Tong ShiAffiliated withDepartment of Pharmacology, Yale University School of Medicine Email author 
  • , Ju BaoAffiliated withDepartment of Structural Biology, St. Jude Children’s Research Hospital Email author 
  • , Nick X WangAffiliated withDepartment of Structural Biology, St. Jude Children’s Research Hospital Email author 
  • , Jie ZhengAffiliated withDepartment of Structural Biology, St. Jude Children’s Research Hospital Email author 
  • , Dianqing WuAffiliated withDepartment of Pharmacology, Yale University School of Medicine Email author 

Abstract

Background

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.

Results

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.

Conclusions

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.