一个 p53 诱导的亡模型
1The Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature
|September 26, 1997
概括
瘤抑制蛋白p53通过一种涉及氧化应激的新三步过程触发了亡. 这一发现揭示了p53的特征.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞死亡机制 细胞死亡机制
背景情况:
- 在人类癌症中,p53瘤抑制基因经常被禁用,这促使人们对其功能进行研究.
- p53表达可以诱导细胞循环停止或细胞亡,但p53依赖性细胞亡的机制尚未完全理解.
- 虽然结直肠癌中p53诱导的生长停止涉及p21WAF1/CIP1,但亡途径在很大程度上仍然没有表征.
研究的目的:
- 为了研究p53的转录点,先于细胞亡.
- 阐明了p53介导的编程细胞死亡的分子机制.
主要方法:
- 用基因表达概况来识别通过p53表达升调的转录.
- 对p53表达细胞与对照细胞中的7202个转录的分析.
- 为了验证发现,进行了生化和药理实验.
主要成果:
- 在7202个转录中,只有14个 (0.19%) 在p53表达时显著增加.
- 预测许多高调的基因参与氧化应激反应.
- 提出了一种由p53诱导的新的三阶段亡途径:氧化还原基因诱导,活性氧物种生成和线粒体损伤.
结论:
- 由于p53诱导的亡是通过转录上调与氧化还原相关基因的调节.
- 反应性氧物种的形成和随后的线粒体的氧化降解是p53-依赖细胞死亡的关键事件.
- 这项研究揭示了p53驱动的亡的新型机制,其中包括氧化应激.
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