Screening for small molecule modulators of SCFbTrCP ubiquitin ligase complex

National Center For Advancing Translational Sciences

Investigators

Abstract

The goal of this project is to identify small molecule modulators of the SCFTrCP complex. SCF E3 ubiquitin ligases are a family of proteins which promote the proteasome-mediated degradation of almost 80% of cellular proteins and play a crucial role in cellular physiology, signaling, and transformation. SCFTrCP is a particularly important member of this family, as it is often deregulated in many types of cancers as well as other diseases. To date, the project team has optimized a cell-based assay that employs a nanoluciferase degron to monitor specific cellular activity of the SCFTrCP complex. Employing this assay, we have completed initial screening of our drug repurposing libraries and have a peer-reviewed manuscript summarizing this work under review. We have also expanded screening of our internal collections and are developing an SCF counterassay to support hit triage.