TRAIL receptor-2 signals apoptosis through FADD and caspase-8
TRAIL receptor-2 signals apoptosis through FADD and caspase-8
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DOI：
10.1038/35008667
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发表时间：
2000-04-01
影响因子：
21.3
通讯作者：
Tschopp, J
中科院分区：
文献类型：
--
作者：
Bodmer, JL;Holler, N;Tschopp, J
*洛桑大学生物化学研究所，BIL生物医学研究中心，Chemin des Boveresses 155, CH-1066 epalings， Switzerland†哈佛医学院细胞生物学系，Boston, Massachusetts 02115, USA‡e-mail: jurg。直到；肿瘤坏死因子（TNF）家族的某些细胞因子及其同源受体（统称死亡受体）是程序性细胞死亡（凋亡）的有效诱导剂1。其中一种蛋白质是细胞表面受体Fas，它在配体结合后，通过Fas的细胞质死亡结构域三聚体并招募接合蛋白FADD。然后FADD结合并激活procaspase-8（参考文献1）。TRAIL是最近发现的TNF死亡配体家族的成员，可在多种肿瘤细胞中诱导细胞凋亡，但在正常细胞中却不能。TRAIL通过两种含有死亡结构域的受体TRAIL- r1（也称为死亡受体（DR） 4） 3和TRAIL- r2（或DR5） 4 - 9诱导细胞凋亡。对trail受体诱导的细胞凋亡的细胞内信号通路的研究产生了有争议的结果。遗传证据10,11表明
* Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland† Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA‡ e-mail: jurg. tschopp@ ib. unil. ch ertain cytokines of the tumour-necrosis factor (TNF) family and their cognate receptors (collectively named death receptors) are potent inducers of programmed cell death (apoptosis) 1. One such protein is the cell-surface receptor Fas, which, upon ligand binding, trimerizes and recruits the adaptor protein FADD through the cytoplasmic death domain of Fas. FADD then binds and activates procaspase-8 (ref. 1). TRAIL, the most recently identified member of the TNF family of death ligands, can induce apoptosis in a wide variety of tumour cells but not in normal cells2. TRAIL induces apoptosis through two death-domain-containing receptors, TRAIL-R1 (also called death receptor (DR) 4) 3 and TRAIL-R2 (or DR5) 4–9. Investigation of the intracellular signalling pathways responsible for TRAIL-receptor-induced apoptosis has produced controversial results. Genetic evidence10, 11 indicates the