氧化诱导的核糖体碰撞激活了核糖体监控机制
Laura Ryder1,2, Frederic Schrøder Arendrup3, José Francisco Martínez1,2
1Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark.
Cell death & disease
|July 26, 2023
概括
氧化 (NO) 爆发减少了蛋白质翻译,导致人类细胞中的核糖体碰撞. 这会激活细胞监控通路,包括核糖毒性应激和综合应激反应.
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
- 生物化学 生物化学
背景情况:
- 核糖体碰撞是蛋白质翻译障碍的结果,触发了细胞监视和救援机制.
- 核糖体碰撞的生理触发,尽管它的随机发生,仍然在很大程度上未定义.
研究的目的:
- 调查氧化 (NO) 作为核糖体碰撞的潜在诱导者的作用.
- 为了阐明NO诱导的核糖体碰撞激活的下游细胞反应.
主要方法:
- 利用人类细胞系研究氧化 (NO) 爆发对蛋白质翻译的影响.
- 分析了压力反应途径的激活,包括 рибо毒性应激反应和综合应激反应.
- 检查了ZAKα介导的激酶激活 (p38,JNK),ZNF598介导的全方位化 (RPS10) 和GCN2激活.
主要成果:
- 已证明,氧化 (NO) 降低了翻译活性,导致人类细胞中的核糖体碰撞.
- NO诱导的核糖体碰撞激活了核糖毒应激反应的ZAKα-p38/JNK轴.
- NO的产生与ZNF598依赖的RPS10无化和GCN2介导的综合应激反应激活相关.
结论:
- 氧化 (NO) 作为人类细胞中的核糖体碰撞的新生理诱导剂.
- NO介导的核糖体碰撞触发了特定的核糖体监测和应激反应途径.
- 这项研究揭示了细胞信号传递 (NO) 与蛋白质翻译保真度调节之间的新联系.
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