Death receptor-induced cell killing

被引:635
作者
Thorburn, A
机构
[1] Wake Forest Univ, Dept Canc Biol, Winston Salem, NC 27157 USA
[2] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27157 USA
基金
美国国家卫生研究院;
关键词
death receptors; TNF; caspase-8;
D O I
10.1016/j.cellsig.2003.08.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Apoptosis pathways activated by death receptors of the tumour necrosis factor (TNF) family such as Fas, TNFR1, or the TRAIL receptors DR4 and DR5 are implicated in diverse diseases. These are also the best-understood apoptosis pathways and many of our ideas about apoptosis, regulation come from studying these pathways. Cell killing from such receptors occurs because of recruitment to the receptor of the adaptor protein FADD, which in turn recruits the pro form of caspase-8. Aggregation of pro-caspase-8 leads to its auto-activation and subsequent activation of effector caspases such as caspase-3. The apoptotic signal can be amplified through the mitochondria and inhibited through the action of competing molecules such as the inhibitor c-FLIP, which binds to the receptor complex in place of caspase-8. This simple mechanism explains much of the cell death that is induced by death receptors. However, recent studies indicate that we must incorporate new information into this model. Some examples that add new layers of complexity will be discussed in this review. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:139 / 144
页数:6
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