在p53-依赖性亡和瘤抑制中的Apaf-1和caspase-9
M S Soengas1, R M Alarcón, H Yoshida
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Science (New York, N.Y.)
|April 2, 1999
概括
瘤抑制剂p53依赖caspase-9和Apaf-1来诱导亡. 这些蛋白质的损失,如p53,通过使瘤基因驱动的细胞存活,促进癌症.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞死亡途径 细胞死亡途径
背景情况:
- 瘤抑制蛋白p53在预防癌症方面发挥着至关重要的作用,通过诱导亡来应对瘤性压力.
- 了解p53-介导的亡的下游作用因子对于理解瘤抑制机制至关重要.
研究的目的:
- 研究caspase-9和Apaf-1作为p53瘤抑制功能的下游调解者的作用,特别是在Myc诱导的亡中.
- 为了确定Apaf-1和caspase-9是否对预防癌基因诱导的细胞增殖和转化至关重要.
主要方法:
- 使用的小鼠胚胎纤维细胞 (MEF) 细胞缺乏p53,Apaf-1和caspase-9.
- 在这些细胞系中表达了瘤基因c-Myc,以研究亡抵抗和瘤转化.
- 在模仿瘤发育的条件下评估细胞对亡刺激的反应.
主要成果:
- 缺乏p53或缺少Apaf-1和caspase-9的MEF细胞表现出对Myc诱导的亡的抵抗力.
- 无活化Apaf-1或caspase-9功能替代p53损失,促进Myc表达细胞中的瘤转化.
- 这些发现强调了Apaf-1/caspase-9通路在p53介导的瘤抑制中的关键参与.
结论:
- Apaf-1和caspase-9是p53的亡途径的必要下游组成部分,对于瘤抑制至关重要.
- Apaf-1/caspase-9轴通过调节亡来响应瘤信号,在控制瘤发育方面发挥着重要作用.
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