一个与多A结合蛋白和EWS的复合物促进前列腺细胞中瘤性ETS转录因子的转录功能
Benjamin M Greulich1, Saranya Rajendran2, Nicholas F Downing2
1Department of Biology, Mercer University, Macon, Georgia, USA.
The Journal of biological chemistry
|November 13, 2023
概括
一项新的研究显示,RNA结合蛋白PABPC1与ERG和EWS相互作用,形成一个复合物,对ERG驱动的前列腺癌至关重要. 针对这个复合体可能为ERG阳性前列腺瘤提供新的治疗策略.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 遗传学 遗传学 是一个
背景情况:
- 在前列腺癌中,ETS转录因子ERG经常过度表达,通常是由于TMPRSS2/ERG基因融合.
- 前列腺细胞中的ERG瘤活性取决于与RNA结合蛋白EWS等协活性剂的相互作用.
研究的目的:
- 研究ERG,EWS之间的相互作用,并确定前列腺癌中的潜在调解因素.
- 阐明PABPC1在ERG介导的瘤发生和转录激活中的作用.
主要方法:
- 同免疫沉测试以确定ERG,EWS和PABPC1.0之间的直接和间接相互作用.
- 西部涂抹和RT-qPCR用于评估蛋白质和基因表达水平.
- 通过RNA免疫沉,然后进行测序 (RIP-seq),以确定基因组结合部位.
- 通过siRNA介导的PABPC1的淘汰,以评估其功能作用.
主要成果:
- ERG 与 EWS 直接和间接地相互作用,间接的相互作用由 PABPC1.1 介导.
- PABPC1直接与ERG和EWS结合在一起.
- ERG表达诱导PABPC1的核定位,并将其招募到ERG/EWS基因组结合点.
- PABPC1倒置抑制了ERG驱动的表型,并降低了ERG的转录激活能力.
结论:
- 确定了一种涉及ERG,EWS和PABPC1的新型综合体,在ERG阳性前列腺癌中发挥关键作用.
- 这种ERG-EWS-PABPC1复合体代表了ERG驱动的前列腺瘤的潜在治疗标.
- 确立了PABPC1在ERG中介转录调节方面以前未知的核功能.
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