The α-chain of the nascent polypeptide-associated complex binds to and regulates FADD function
The α-chain of the nascent polypeptide-associated complex binds to and regulates FADD function
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DOI：
10.1016/s0006-291x(03)00487-x
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发表时间：
2003-04
影响因子：
3.1
通讯作者：
R. Stilo;D. Liguoro;B. Jeso;A. Leonardi;P. Vito
中科院分区：
文献类型：
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作者：
R. Stilo;D. Liguoro;B. Jeso;A. Leonardi;P. Vito
FADD蛋白是由TNF受体基因超家族的几个成员激活的信号转导途径的关键介质。最近，诱导邻近模型已被提出来解释FADD介导的信号事件。根据该模型，FADD通过在活化的受体复合物附近诱导效应分子簇来促进信号传导。诱导邻近模型的一个重要推论是FADD蛋白在没有受体刺激的情况下不应形成寡聚体。在这里，我们表明，在死亡受体刺激的情况下，FADD被发现与新生多肽相关复合物（NAC）的α链相关。暴露于TNF导致FADD/NAC复合物的破坏。NAC的表达调节FADD寡聚体的形成并调节FADD介导的信号传导。因此，我们的观察表明，NAC可能作为FADD功能的细胞内调节剂。
FADD protein is a critical mediator of signal transduction pathways activated by several members of the TNF-receptor gene superfamily. Recently, an induced proximity model has been proposed to interpret FADD-mediated signaling events. According to this model, FADD facilitates signaling by inducing clusters of effector molecules in proximity of the activated receptor complex. An important corollary of the induced-proximity model is that FADD protein should not form oligomers in the absence of receptor stimulation. Here we show that, in the absence of death receptor stimulation, FADD is found associated to the α chain of the nascent polypeptide-associated complex (NAC). Exposure to TNF results in disruption of FADD/NAC complex. Expression of NAC regulates formation of FADD oligomers and modulates FADD-mediated signaling. Thus, our observation indicates that NAC may serve as an intracellular regulator of FADD function.