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.

中文翻译：

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用序列特异性 DNA 结合聚酰胺抑制 ERRα 的转录活性

孤儿核受体雌激素相关受体（ERR）与雌激素相关受体反应元件（ERRE）结合，调节细胞代谢和癌细胞生长中的转录程序。在这项研究中，我们评估了吡咯-咪唑聚酰胺阻断 ERRα 与 ERRE 结合从而抑制基因表达的潜力。我们证明，ERRE 靶向聚酰胺 1 阻断了 ERRα 与共有 ERRE 的结合，并降低了细胞培养物中 ERRα 的转录活性。我们进一步表明，用聚酰胺 1 抑制 ERRα 转录活性会导致线粒体耗氧量减少，这是 ERRα 调节的主要生物效应。最后，我们的数据表明聚酰胺 1 是癌细胞生长的抑制剂。