NCBP1压力信号驱动替代S6K1拼接抑制翻译
Dalu Chang1,2, Mahdi Assari3, Chananya Suwathep4
1University of Oxford, Oxford, UK.
Nature chemical biology
|February 10, 2026
概括
核中的局部电友应力阻碍了蛋白质合成. 在cysteine 436中核定居的NCBP1蛋白质的修饰通过SF3A1相互作用破坏引发了广泛的替代拼接和翻译抑制.
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:
- 亚细胞应激会影响蛋白质合成,但特定的化学线索和局部蛋白质反应尚未得到充分理解.
- 绘制局部特异性应激反应器及其对蛋白质组合成的功能影响至关重要.
研究的目的:
- 研究局部电友应激对不同亚细胞区分的蛋白质合成的影响.
- 识别对核应激有反应的特定蛋白质,并阐明它们的作用机制.
主要方法:
- 精确局部电友生成和遗传代码扩展工具的整合.
- 活体系统中的应激反应蛋白在四个亚细胞区域的功能映射.
- 分析蛋白质修饰,蛋白质与蛋白质相互作用以及对基因表达和翻译的下游影响.
主要成果:
- 核向电应激,但在其他检查的区域没有应激,阻碍了蛋白质的翻译.
- 核定居的NCBP1蛋白通过修改单个氨酸 (C436) 来传播压力信号.
- NCBP1(C436) 修改导致了250多个基因的替代拼接,并与SF3A1,一个拼接体组件的关联受损.
结论:
- NCBP1(C436) 修饰是核电应力反应的关键调解者.
- 修改后的NCBP1和SF3A1之间的相互作用中断触发了一连串,导致S6激酶的产生和全球蛋白质合成的抑制.
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