FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2
FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2
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DOI：
10.1016/s1074-7613(00)80211-3
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发表时间：
2000-06-01
期刊：
影响因子：
32.4
通讯作者：
Walczak, H
中科院分区：
文献类型：
--
作者：
Sprick, MR;Weigand, MA;Walczak, H
肿瘤坏死因子 (TNF) 相关凋亡诱导配体 (TRAIL/APO-2L) 诱导的细胞凋亡已被证明在各种免疫过程中发挥重要功能。死亡衔接蛋白 FADD/MORT1、TRADD 和 RIP 以及启动凋亡的 caspase-8 和 -10 在两种死亡诱导 TRAIL 受体 1 和 2（TRAIL-R1 和 TRAIL-R2）的死亡信号传导中的参与存在争议。对天然 TRAIL 死亡诱导信号复合物 (DISC) 的分析揭示了 FADD/MORT1 和 caspase-8 的配体依赖性募集。配体刺激的 TRAIL 受体的差异沉淀表明 FADD/MORT1 和 caspase-8 彼此独立地被招募到 TRAIL-R1 和 TRAIL-R2。仅表达 TRAIL-R2 的 FADD/MORT1 和 caspase-8 缺陷 Jurkat 细胞对 TRAIL 诱导的细胞凋亡具有抵抗力。因此，FADD/MORT1 和 caspase-8 对于通过 TRAIL-R2 诱导细胞凋亡至关重要。
Apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/APO-2L) has been shown to exert important functions during various immunological processes. The involvement of the death adaptor proteins FADD/MORT1,TRADD, and RIP and the apoptosis-initiating caspases-8 and -10 in death signaling by the two death-inducing TRAIL receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are controversial. Analysis of the native TRAIL death-inducing signaling complex (DISC) revealed ligand-dependent recruitment of FADD/MORT1 and caspase-8. Differential precipitation of ligand-stimulated TRAIL receptors demonstrated that FADD/MORT1 and caspase-8 were recruited to TRAIL-R1 and TRAIL-R2 independently of each other. FADD/MORT1- and caspase-8-deficient Jurkat cells expressing only TRAIL-R2 were resistant to TRAIL-induced apoptosis. Thus, FADD/MORT1 and caspase-8 are essential for apoptosis induction via TRAIL-R2.