Identification Of Small Molecule TRABID Deubiquitinase Inhibitors By Computation-Based Virtual Screen
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.
- Identification Of Small Molecule TRABID Deubiquitinase Inhibitors By Computation-Based Virtual Screen
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
BMC Chemical Biology
- Online Date
- May 2012
- Online ISSN
- BioMed Central
- Additional Links