通过条件删除40S核糖体蛋白S6来阻止增殖,但不能阻止生长
S Volarevic1, M J Stewart, B Ledermann
1Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
Science (New York, N.Y.)
|June 17, 2000
概括
核糖体生物生成对于细胞生长至关重要. 在小鼠肝脏中破坏40S核糖体的产生意外地允许生长,但阻断了细胞增殖,这表明细胞循环的检查点.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 核糖体生物发生对于细胞增殖至关重要.
- 可能存在细胞机制来检测和响应核糖体生产中断.
- 40S核糖体蛋白S6对于40S核糖体的生物生成至关重要.
研究的目的:
- 研究40S核糖体生物发生在肝细胞增殖和细胞周期控制中的作用.
- 为了确定核糖体生物发生的缺陷是否会触发检查点反应.
主要方法:
- 在成年老鼠肝脏中,对编码40S核糖体蛋白S6的基因有条件删除.
- 禁食和营养补充的协议.
- 部分肝切除术以诱导肝脏再生.
- 对细胞增殖标记物 (如环林E) 和细胞循环复合物 (如环林D-CDK4) 的分析.
主要成果:
- 缺乏40S核糖体蛋白S6的肝脏表现出营养驱动的增长,尽管废除了核糖体生物发生.
- 在部分肝切除术后,肝细胞无法增殖或诱导环林E的表达.
- 形成了活性环林D-CDK4复合体,但细胞循环进展被抑制.
结论:
- 40S核糖体生物生成的废除可以诱导一个检查点控制,防止细胞循环的进展.
- 这表明有监控机制将核糖体生产与细胞周期调节联系起来.
- 核糖体生物生成的干扰会阻碍肝细胞的增殖,而不依赖于营养的可用性.
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