A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.

Autor: Taylor R Nicholas, Jingwei Meng, Benjamin M Greulich, Teresa Stevie Morris, Peter C Hollenhorst
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS ONE, Vol 15, Iss 9, p e0238999 (2020)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0238999
Popis: Aberrant expression of the transcription factor ERG is a key driving event in approximately one-half of all of prostate cancers. Lacking an enzymatic pocket and mainly disordered, the structure of ERG is difficult to exploit for therapeutic design. We recently identified EWS as a specific interacting partner of ERG that is required for oncogenic function. In this study, we aimed to target this specific protein-protein interaction with small molecules. A high-throughput screening (HTS) strategy was implemented to identify potential protein-protein interaction inhibitors. Secondary assays verified the function of several hit compounds, and one lead compound inhibited ERG-mediated phenotypes in prostate cells. This is the first study aimed at targeting the ERG-EWS protein-protein interaction for the development of a small molecule-based prostate cancer therapy.
Databáze: Directory of Open Access Journals
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