Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

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


ABSTRACT: 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. Examination of ERG in VCaP cells with respect to peptidomimetics treatment

ORGANISM(S): Homo sapiens

SUBMITTER: Arul Chinnaiyan 

PROVIDER: E-GEOD-58939 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

Similar Datasets

2014-07-15 | E-GEOD-58940 | biostudies-arrayexpress
2014-07-15 | GSE58939 | GEO
2014-05-21 | E-GEOD-49091 | biostudies-arrayexpress
2013-06-13 | E-GEOD-47120 | biostudies-arrayexpress
2016-03-22 | E-GEOD-79491 | biostudies-arrayexpress
2010-07-07 | E-MEXP-2759 | biostudies-arrayexpress
2014-07-15 | GSE58940 | GEO
2013-06-13 | E-GEOD-47119 | biostudies-arrayexpress
2014-04-25 | E-GEOD-55062 | biostudies-arrayexpress
2018-08-02 | GSE110656 | GEO