Scholarlink

<p>The inhibition of estrogen receptor (ER)-mediated genomic signaling in ER-positive cancer cells has long been a primary focus of therapeutic strategies. Here, we introduce a switchable competitive inhibition system for ERα-mediated transcriptional regulation, termed DOCTER (<Emphasis Type="Underline">D</Emphasis>rug-induced <Emphasis Type="Underline">O</Emphasis>n-Off <Emphasis Type="Underline">C</Emphasis>ompetitor for <Emphasis Type="Underline">T</Emphasis>ranscription mediated by <Emphasis Type="Underline">ER</Emphasis>α). DOCTER integrates the Tet-On induced Cre-<i>lox</i>P recombination system to enable precise, reversible on/off switching. We demonstrate that DOCTER effectively inhibits ERα-mediated transcriptional regulation in breast cancer cells, modulating both exogenous and endogenous gene expression, and remains effective in cells harboring ERα ligand-binding domain (LBD) mutations. Upon drug induction, DOCTER exhibits controllable and reversible inhibition. To visualize these dynamic switching events in real time, we developed a multi-color fluorescent reporting system that enables monitoring of complete DOCTER switch-off within 24 hours. Our study provides a novel approach for time-specific transcriptional regulation and offers broad potential for applications in genetic research and therapeutic development.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

DOCTER: a genetically encoded switchable protein module for ERα-mediated transcriptional regulation

  • 期刊论文

  • 发表日期：

    2026年5月26日

查看全文
  • Jinmin Wang,
  • Jingfang Liu,
  • Dandan Peng,
  • Yuhao Ji,
  • Ke Huang,
  • Junfen Fu,
  • Yingke Xu

摘要

The inhibition of estrogen receptor (ER)-mediated genomic signaling in ER-positive cancer cells has long been a primary focus of therapeutic strategies. Here, we introduce a switchable competitive inhibition system for ERα-mediated transcriptional regulation, termed DOCTER (Drug-induced On-Off Competitor for Transcription mediated by ERα). DOCTER integrates the Tet-On induced Cre-loxP recombination system to enable precise, reversible on/off switching. We demonstrate that DOCTER effectively inhibits ERα-mediated transcriptional regulation in breast cancer cells, modulating both exogenous and endogenous gene expression, and remains effective in cells harboring ERα ligand-binding domain (LBD) mutations. Upon drug induction, DOCTER exhibits controllable and reversible inhibition. To visualize these dynamic switching events in real time, we developed a multi-color fluorescent reporting system that enables monitoring of complete DOCTER switch-off within 24 hours. Our study provides a novel approach for time-specific transcriptional regulation and offers broad potential for applications in genetic research and therapeutic development.