THE TNF RECEPTOR 1-ASSOCIATED PROTEIN TRADD SIGNALS CELL-DEATH AND NF-KAPPA-B ACTIVATION
THE TNF RECEPTOR 1-ASSOCIATED PROTEIN TRADD SIGNALS CELL-DEATH AND NF-KAPPA-B ACTIVATION
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DOI：
10.1016/0092-8674(95)90070-5
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发表时间：
1995-05-19
期刊：
影响因子：
64.5
通讯作者：
GOEDDEL, DV
中科院分区：
文献类型：
--
作者：
HSU, HL;XIONG, J;GOEDDEL, DV
肿瘤坏死因子（TNF）的许多不同活性通过TNF受体1（TNFR 1）发出信号。我们已经确定了一种新的34 kDa的蛋白质，指定TRADD，特异性相互作用的TNFR 1的细胞内结构域已知是必不可少的介导程序性细胞死亡。TRADD的过表达导致两种主要的TNF诱导的应答，即凋亡和NF-κ B的活化。TRADD的C-末端118个氨基酸足以触发这两种活性，并且同样足以与TNFR 1的死亡结构域相互作用。TRADD介导的细胞死亡可以被crmA基因抑制，该基因编码白细胞介素-1 β转化酶的特异性抑制剂。然而，TRADD对NF-κ B的激活不受crmA表达的抑制，表明TNF诱导的细胞死亡和NF-κ B激活的信号传导途径是不同的。
Many diverse activities of tumor necrosis factor (TNF) are signaled through TNF receptor 1 (TNFR1). We have identified a novel 34 kDa protein, designated TRADD, that specifically interacts with an intracellular domain of TNFR1 known to be essential for mediating programmed cell death. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa B. The C-terminal 118 amino acids of TRADD are sufficient to trigger both of these activities and likewise sufficient for interaction with the death domain of TNFR1. TRADD-mediated cell death can be suppressed by the crmA gene, which encodes a specific inhibitor of the interleukin-1 beta-converting enzyme. However, NF-kappa B activation by TRADD is not inhibited by crmA expression, demonstrating that the signaling pathways for TNF-induced cell death and NF-kappa B activation are distinct.