Repression of the transcriptional activity of ERRα with sequence-specific DNA-binding polyamides.
Chien-Yu ChenYang LiTiezheng JiaLina HeAlissa A HareAmanda SilbersteinJohn GallagherThomas F MartinezBangyan L StilesBogdan OlenyukPeter B DervanBangyan L StilesPublished in: Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents (2020)
The orphan nuclear receptors estrogen-related receptors (ERRs) bind to the estrogen-related receptor response element (ERRE) to regulate transcriptional programs in cellular metabolism and cancer cell growth. In this study, we evaluated the potential for a pyrrole-imidazole polyamide to block ERRα binding to ERREs to inhibit gene expression. We demonstrated that the ERRE-targeted polyamide 1 blocked the binding of ERRα to the consensus ERRE and reduced the transcriptional activity of ERRα in cell culture. We further showed that inhibiting ERRα transcriptional activity with polyamide 1 led to reduced mitochondrial oxygen consumption, a primary biological effect regulated by ERRα. Finally, our data demonstrated that polyamide 1 is an inhibitor for cancer cell growth.