激素诱导增强剂组装需要一个最佳水平的激素受体多价值相互作用
Lizhen Chen1, Zhao Zhang2, Qinyu Han3
1Department of Molecular Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Barshop Institute for Longevity and Aging Studies, Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Molecular cell
|September 22, 2023
概括
雄激素受体 (AR) 使用其内在无序区域 (IDR) 形成凝聚物,为基因调节编排增强剂组合. 最佳AR凝结对于转录活动至关重要,与AR相关疾病相关的干扰.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 转录因子 (TFs) 通过激活增强剂来调节细胞特异性基因表达.
- 在信号事件期间增强器组装的精确机制尚未完全理解.
研究的目的:
- 为了研究雄激素受体 (AR) 内在失序区域 (IDR) 在雄激素信号传递期间增强器组装中的作用.
- 确定AR凝结如何影响转录活动及其与人类病理学的潜在联系.
主要方法:
- 活细胞单分子显微镜测量AR凝结倾向.
- 测试以评估AR凝结能力和功能的增强器.
- 研究AR与其他增强剂成分的异型多价值相互作用.
主要成果:
- 通过其N端IDR调解的多价值相互作用,AR通过对雄激素信号的响应形成凝结物.
- 通过替换其他IDR或通过改变poly (Q) 轨道长度来调节AR IDR的冷凝能力.
- 弱化和强化的AR凝结都会损害增强剂组合和转录活性.
结论:
- 一个最佳的AR凝结水平对于调解增强器组装至关重要.
- 对AR多价值IDR-IDR相互作用的失调可能会导致AR相关的人类疾病.
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