Bryan Berteaux III
Pronouns: He, His
Research Mentor(s): George WANG
Co-Presenter:
Research Mentor School/College/Department: Pathology-MCTP / Medicine
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 6 – 4:40pm – 5:30 pm
Room: Breakout room 6
Authors:
Presenter: 1
Abstract
Transcription factors play a key role in the development of diverse cancers. In prostate cancer, more than 50% of patients harbor recurrent TMPRSS2:ERG gene fusion, which drives a unique transcriptional program in prostate oncogenesis. Recently, we identified a series of peptides that interact specifically with the DNA binding domain of ERG [5]. ERG inhibitory peptides (EIPs) bound to ERG with high affinity and specificity, thus disrupting ERG protein-protein interactions in vitro. Cell-permeable EIPs conjugated with the cationic HIV-TAT motif specifically inhibit ERG binding to target loci, disrupt ERG transcriptional activity. Interestingly EIPs binding leads to proteolytic degradation of the ERG protein, therefore blocking ERG-mediated cell invasion and proliferation. Finally, a retroinverso version of the peptides suppresses tumor growth in vivo. The observation that EIPs destabilize ERG protein highlights an alternative approach to therapeutic modulation of transcription factors. Unlike small-molecule antagonists that continuous dosing often induces drug resistance, target degraders usually have higher and longer pharmacological effects without requiring continuous high exposure. Such an approach can abolish the presence of an oncoprotein, which, in theory, can overcome resistance to target inhibitors.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
