空间分辨率MYC的光近距离分析确定了癌细胞中的MYC-BAF负债
Anthony J Carlos1, Shuyuan Huang1, Dongbo Yang1
1Department of Chemistry, The University of Chicago. Chicago, IL, 60637, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
使用siPROX绘制与c-MYC转录因子的蛋白质相互作用,揭示了它与BAF复合体的关联. 抑制BAF复合物降低了MYC水平和癌细胞中的增殖,这表明了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- c-MYC转录因子的异常表达驱动了许多人类癌症的扩散.
- 了解MYC在其调节复合体内的蛋白相互作用,对于确定治疗点至关重要.
- 由于其复杂的结构和相互作用,以前的方法在定义特定上下文的MYC交互器方面面临着挑战.
研究的目的:
- 开发和应用一种新的方法来绘制细胞内的MYC中心蛋白质复合物拓.
- 在疾病相关模型中识别上下文依赖的MYC交互体.
- 探索针对MYC驱动癌症中MYC蛋白相互作用的治疗潜力.
主要方法:
- 开发一对相匹配的光近距离探头,用于细胞内测绘.
- 应用空间分辨率,细胞内光近距离 (siPROX) 分析以及定量蛋白质组学.
- 在时间,空间和疾病相关的环境中分析MYC互动组,包括抑制剂治疗.
主要成果:
- siPROX成功地绘制出已知的MYC相互作用体,并揭示了在抑制剂治疗后转录调节者的动态重塑.
- 该研究确定了与BAF复合体成员 (例如,PBRM1,SMARCC1) 的持续相互作用,即使与odomain抑制.
- 抑制BAF复合ATPase活性 (SMARCA2/4) 导致MYC水平降低,MYC依赖转录减少,癌细胞生长受损.
结论:
- siPROX技术有效地识别了空间解析的动态转录因子相互作用体.
- 与BAF复合体的MYC相互作用在MYC驱动的癌症中代表了一个可向的漏洞.
- 针对MYC-BAF相互作用提供了一个潜在的策略来调节MYC依赖的转录和扩散.
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