这种TNF受体1关联蛋白TRADD信号细胞死亡和NF-kappa B激活
1Tularik, Incorporated, South San Francisco, California 94080, USA.
Cell
|May 19, 1995
概括
研究人员发现TRADD是一种与TNF受体1 (TNFR1) 相互作用的蛋白质. TRADD触发了瘤亡因子 (TNF) 诱导的亡和NF-kappa B激活,揭示了不同的信号通路.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 免疫学 免疫学 免疫学
背景情况:
- 瘤亡因子 (TNF) 通过TNF受体1 (TNFR1) 引起各种细胞反应.
- 了解TNFR1下游的细胞内信号传导机制对于破译TNF介导的生物结果至关重要.
- 编程细胞死亡和炎症反应是TNF诱导的关键途径.
研究的目的:
- 为了确定参与TNFR1信号传递的新型蛋白质.
- 阐明TRADD在调解TNF诱导的亡和NF-kappa B激活中的作用.
- 为了区分控制细胞死亡和NF-kappa B激活的信号通路,下游的TNFR1.1.
主要方法:
- 蛋白质与蛋白质相互作用的研究,以确定TRADD与TNFR1.1结合.
- 过度表达TRADD及其C端域以评估功能后果.
- 利用crmA基因,一个抑制因特乐金-1β转化酶的抑制剂,探测信号通路.
主要成果:
- 一种新的34 kDa蛋白,TRADD,被确定,它特别结合TNFR1.1的细胞内死亡域.
- 过度表达TRADD诱导了TNF介导的亡和NF-kappa B激活.
- 对于TNFR1相互作用和诱导两个细胞反应,TRADD的C端118氨基酸足够.
- TRADD诱导的亡被crmA抑制,而NF-kappa B激活没有,表明不同的途径.
结论:
- TRADD是TNFR1信号传递的关键媒介,将受体连接到亡和NF-kappa B通路.
- TNF诱导的编程细胞死亡和NF-kappa B激活的信号级联在TRADD的下游分离.
- 在对TNF刺激的反应中,TRADD代表了决定细胞命运的关键分子开关.
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