title: Identification Of Small Molecule TRABID Deubiquitinase Inhibitors By Computation-Based Virtual Screen.
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.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Shi
authors.affiliation: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Nick X
authors.initials: NX
authors.lastname: Wang
authors.affiliation: Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Dianqing
authors.initials: D
authors.lastname: Wu