Development of peptidomimetic inhibitors of the ERG transcription factor in prostate cancer (ChIP-seq)

Transcription factors play a key role in the development of a number of cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the ETS transcription factor ERG is recurrently rearranged and likely plays a critical role in prostate oncogenesis. Here we identified a series of peptides from a phage-display library that interact specifically with the DNA binding domain of ERG. The interactive interface was mapped to 9-residues in the 3rd helix of the ETS domain that is critical for ERG transcriptional activity. The peptides were found to efficiently disrupt ERG-mediated protein-protein interactions, transcription, DNA damage, and cell invasion, as well as attenuate ERG recruitment to target gene loci. Furthermore, a retroinverso peptidomimetic version of the peptide sequence suppressed tumor growth, intravasation, and metastasis in vivo. Taken together, our results demonstrate that transcription factors have specific residues important for protein-protein interactions and disrupting those critical interactions may be an effective therapeutic strategy.

Dataset features

Information

Specifications

Application:	ChIP-seq analysis
Number of samples:	2
Release date:	Jul 15 2014
Last update date:	Oct 24 2018
Access:	Public
Diseases:	Neoplasms, Prostatic Neoplasms
Genes:	ERG
Dataset link	Development of peptidomimetic inhibitors of the ERG transcription factor in prostate cancer (ChIP-seq)

Experimental Protocol

Examination of ERG in VCaP cells with respect to peptidomimetics treatment

Repositories

GEO

ArrayExpress

ENA

BioProject

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Contact

Xiaoju Wang