A cell-based high-throughput screening method based on a ubiquitin-reference technique for identifying modulators of E3 ligases.

ABSTRACT: Accumulating evidence indicates that a wide range of E3 ubiquitin ligases are involved in the development of many human diseases. Searching for small-molecule modulators of these E3 ubiquitin ligases is emerging as a promising drug discovery strategy. Here, we report the development of a cell-based high-throughput screening method to identify modulators of E3 ubiquitin ligases by integrating the ubiquitin-reference technique (URT), based on a fusion protein of ubiquitin located between a protein of interest and a reference protein moiety, with a Dual-Luciferase system. Using this method, we screened for small-molecule modulators of SMAD ubiquitin regulatory factor 1 (SMURF1), which belongs to the NEDD4 family of E3 ubiquitin ligases and is an attractive therapeutic target because of its ro

SUBMITTER: Tian M 

PROVIDER: S-EPMC6393603 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature