对于TNFalpha诱导的亡,需要一个依赖JNK的途径
Yibin Deng1, Xiaoyang Ren, Lin Yang
1Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 70030, USA.
Cell
|October 9, 2003
概括
瘤亡因子 (TNFalpha) 信号激活了JNK,它分裂了Bid. 这释放了Smac/DIABLO,缓解了抑制,并使亡的caspase 8激活.
科学领域:
- 细胞信号传递途径 细胞信号传递途径
- 细胞亡和细胞死亡机制.
- TNFalpha信号传递的分子生物学
背景情况:
- 瘤亡因子-α (TNFalpha) 受体信号激活多个下游效应因子,包括caspase8,NF-kappaB和JNK.
- 虽然酶8对于TNFalpha诱导的亡是必不可少的,NF-kappaB抑制细胞死亡,但JNK在这种途径中的作用尚不清楚.
研究的目的:
- 为了阐明JNK激活在TNFalpha介导的亡中的精确功能.
- 定义连接JNK激活到酶8分裂和细胞死亡的顺序途径.
主要方法:
- 使用分子生物学技术研究了JNK,Bid和Smac/DIABLO在TNFalpha信号传递中的作用.
- 分析了caspase 8裂变,Bid裂变产物生成 (jBid) 和线粒体蛋白质的释放.
- 检查了Smac/DIABLO对TRAF2-cIAP1复合物的干扰.
主要成果:
- 通过TNFalpha介导的亡需要一个涉及JNK,Bid和Smac/DIABLO的顺序途径.
- 简基因激活导致Bid的酶8独立裂变,产生jBid.
- jBid转移到线粒体导致Smac/DIABLO释放,这破坏了TRAF2-cIAP1复合体.
结论:
- 该JNK通路对于缓解TRAF2-cIAP1-介导的caspase8激活和亡的抑制至关重要.
- 这项研究揭示了内在和外在细胞死亡途径之间的交叉通话的新机制.
- 这些发现为调节TNFalpha诱导的细胞死亡提供了新的见解.
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