核糖体碰撞引发一般应激反应 调节细胞命运
Colin Chih-Chien Wu1, Amy Peterson2, Boris Zinshteyn1
1Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|July 2, 2020
概括
核糖体碰撞引发细胞应激反应,激活应激蛋白激酶 (SAPK) 和GCN2通路. 这种蛋白质作为碰撞的传感器, 立即发出信号.
科学领域:
- 分子生物学
- 细胞信号传输
- 应对压力的途径
背景情况:
- mRNA翻译问题导致核糖体停滞和碰撞,启动细胞质量控制.
- 对核糖体碰撞的更广泛的细胞反应在很大程度上仍未被探索.
研究的目的:
- 调查全球细胞对核糖体碰撞的反应.
- 确定将核糖体碰撞与信号转导联系起来的分子机制.
主要方法:
- 使用翻译延长抑制剂和细胞应激条件 (氨基酸饥饿,紫外线照射).
- 采用了选择性核糖体分析和生物化学分析.
- 研究了MAPKKK ZAK蛋白的作用.
主要成果:
- 核糖体碰撞激活了压力激活蛋白激酶 (SAPK) 和GCN2介导的压力反应.
- 这种MAPKKK ZAK蛋白可以作为核糖体碰撞的传感器.
- ZAK在双胞胎体 (最小碰撞的核糖体单元) 上自化,对SAPK和GCN2的激活至关重要.
结论:
- 核糖体碰撞被认为是信号转导通路的关键触发因素.
- ZAK是一种关键的哨兵蛋白质,可检测核糖体碰撞并启动压力信号.
- 这些发现提供了分子洞察力,了解转化恒常的干扰如何影响细胞命运.
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