NF-kappaB在p53介导的细胞死亡中的作用
K M Ryan1, M K Ernst, N R Rice
1Regulation of Cell Growth Laboratory, NCI-FCRDC, Frederick, Maryland 21702-1201, USA.
Nature
|April 29, 2000
概括
瘤抑制剂p53通过激活NF-kappaB来诱导细胞亡,NF-kappaB是p53-介导细胞死亡的关键因素. 在野生型p53瘤中抑制NF-kappaB可能会降低治疗效果.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞信号传输 细胞信号传输
背景情况:
- 这种p53瘤抑制剂对于通过细胞循环停止和亡来抑制细胞生长至关重要.
- 在许多癌症中,p53的突变或其诱导缺陷是常见的.
- 核因子-卡帕B (NF-kappaB) 是一个关键的转录因子,调节了亡反应.
研究的目的:
- 在亡的背景下调查p53诱导和NF-kappaB激活之间的关系.
- 确定NF-kappaB在p53介导的细胞死亡中的作用.
- 阐明参与p53诱导NF-kappaB激活的信号通路.
主要方法:
- 在癌细胞中诱导p53.
- 评估NF-kappaB激活的情况.
- 抑制NF-kappaB活动和MEK1.
- 诱导亡的分析.
主要成果:
- 诱导p53激活NF-kappaB,与亡相关.
- NF-kappaB对于p53诱导的亡是必不可少的;它的抑制会废除细胞死亡.
- 通过p53介导的NF-kappaB激活涉及MEK1和pp90rsk,不同于TNF-alpha.
- 抑制MEK1阻断了NF-kappaB的激活和p53诱导的细胞死亡.
结论:
- 对于p53介导的亡,NF-kappaB是必不可少的.
- 这条路径涉及MEK1和pp90rsk.
- 在野生型p53瘤中抑制NF-kappaB可能会降低治疗反应.
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