翻译能力的剂量依赖开关控制了转录因子对H2O2压力反应的反应
bioRxiv : the preprint server for biology
|February 9, 2026
概括
高氧化物 (H2O2) 压力抑制蛋白质合成,阻断转录因子 (TF) 积累. 以前存在的TFs穿到核中,为严重的氧化应激提供备用反应.
科学领域:
- 分子生物学分子生物学
- 细胞应激反应的应激反应
- 氧化应激信号 氧化应激信号
背景情况:
- 过氧化 (H2O2) 是细胞压力的关键媒介.
- 转录因子 (TFs) 在细胞对氧化应激反应中起着至关重要的作用.
- 由H2O2对TFs的剂量依赖激活表明了复杂的调节机制.
研究的目的:
- 研究在不同过氧化 (H2O2) 应激水平下控制转录因子 (TF) 积累的调控机制.
- 阐明转化控制在细胞对氧化应激反应中的作用.
- 在严重的H2O2诱导转化抑制期间识别替代TF激活途径.
主要方法:
- 细胞的剂量依赖的H2O2处理.
- 对TF积累和局部化的分析.
- 翻译启动和延长的研究.
- 评估综合应激反应 (ISR),mTORC1信号和eEF2K激活.
主要成果:
- 低H2O2允许积累像p53,NRF2和ATF4这样的TF,驱动基因表达.
- 高H2O2通过ISR,mTORC1抑制和eEF2K激活诱导转化抑制,阻断TF合成.
- 预先存在的TFs (FOXO1,NFAT1,NF-κB) 在高H2O2压力时发生核穿,当翻译被抑制时.
结论:
- 翻译控制是调节TF对H2O2压力的反应的关键开关.
- 高H2O2压力利用先前存在的TFs通过核穿作为备用响应时 de novo蛋白质合成被阻止.
- 了解这些机制,可以了解细胞适应严重的氧化条件.
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