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

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

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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 interactin...

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Main Authors: Taylor R Nicholas, Jingwei Meng, Benjamin M Greulich, Teresa Stevie Morris, Peter C Hollenhorst
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0238999
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spelling doaj-769877bbe6ef46a58b453f88142399e82021-03-04T12:55:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01159e023899910.1371/journal.pone.0238999--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 HollenhorstAberrant 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.https://doi.org/10.1371/journal.pone.0238999
collection DOAJ
language English
format Article
sources DOAJ
author Taylor R Nicholas
Jingwei Meng
Benjamin M Greulich
Teresa Stevie Morris
Peter C Hollenhorst
spellingShingle Taylor R Nicholas
Jingwei Meng
Benjamin M Greulich
Teresa Stevie Morris
Peter C Hollenhorst
--A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.
PLoS ONE
author_facet Taylor R Nicholas
Jingwei Meng
Benjamin M Greulich
Teresa Stevie Morris
Peter C Hollenhorst
author_sort Taylor R Nicholas
title --A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.
title_short --A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.
title_full --A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.
title_fullStr --A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.
title_full_unstemmed --A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.
title_sort --a high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor erg and the cofactor ews.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2020-01-01
description 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.
url https://doi.org/10.1371/journal.pone.0238999
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