--A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.
Taylor R NicholasJingwei MengBenjamin M GreulichTeresa Stevie MorrisPeter C HollenhorstPublished in: PloS one (2020)
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.
Keyphrases
- protein protein
- small molecule
- transcription factor
- high throughput
- prostate cancer
- cancer therapy
- benign prostatic hyperplasia
- poor prognosis
- induced apoptosis
- drug delivery
- dna binding
- genome wide
- climate change
- dna methylation
- nitric oxide
- single cell
- hiv infected
- cell death
- signaling pathway
- hepatitis c virus
- antiretroviral therapy
- long non coding rna
- protein kinase
- childhood cancer
- pi k akt