|
| Status |
Public on Jul 15, 2014 |
| Title |
Development of peptidomimetic inhibitors of the ERG transcription factor in prostate cancer (ChIP-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| |
|
| Overall design |
Examination of ERG in VCaP cells with respect to peptidomimetics treatment
|
| |
|
| Contributor(s) |
Cieslik M, Wang X |
| Citation(s) |
28344039 |
| Submission date |
Jun 30, 2014 |
| Last update date |
Oct 24, 2019 |
| Contact name |
Xiaoju Wang |
| E-mail(s) |
xiaojuw@umich.edu
|
| Phone |
734-763-6056
|
| Organization name |
University of Michigan
|
| Street address |
1500 E. Medical Center Drive
|
| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (2) |
|
| This SubSeries is part of SuperSeries: |
| GSE58975 |
Development of peptidomimetic inhibitors of the ERG gene fusion product in prostate cancer |
|
| Relations |
| BioProject |
PRJNA254028 |
| SRA |
SRP043992 |
