鼠的caspase-11是一种与ICE相互作用的蛋白酶,对于ICE的激活至关重要
1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|March 10, 1998
概括
卡斯帕斯-11 (casp-11) 基因失活使小鼠对内毒性休克产生抵抗力. 卡斯巴-11对介素-1转化酶 (ICE) 激活至关重要,这表明它是关键.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 细胞死亡研究 细胞死亡研究
背景情况:
- 冰/Ced-3 (caspase) 基因家族在编程细胞死亡中起着至关重要的作用.
- 介素-1转化酶 (ICE) 激活是炎症反应 (如败血症休克) 中的一个关键事件.
研究的目的:
- 调查酶-11 (casp-11) 在细胞死亡途径和炎症反应中的作用.
- 为了确定casp-11是否参与ICE的激活.
主要方法:
- 基因向制造CASP-11突变小鼠.
- 对突变小鼠内毒性冲击抗性的分析.
- 在脂多糖刺激后对IL-1α和IL-1β的产生进行评估.
- 使用casp-11突变胚胎纤维细胞的亡测定.
- 共同免疫沉用于研究pro-caspase-11和pro-ICE之间的蛋白质相互作用.
主要成果:
- 卡斯普-11突变小鼠对脂聚糖诱导的内毒性冲击具有抗性.
- 在Casp-11突变小鼠中,在脂多糖刺激后,IL-1α和IL-1β的产生被阻断.
- 卡斯普-11突变细胞对ICE过度表达诱导的亡具有抵抗力.
- 在细胞中,pro-caspase-11与pro-ICE进行物理相互作用.
- 卡斯帕酶-11表达对于ICE激活至关重要.
结论:
- 卡斯帕斯-11是ICE复合体中必不可少的组成部分.
- 酶-11是激活ICE所需的,在炎症信号和细胞死亡中起着至关重要的作用.
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