Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling
Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling
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DOI：
10.1073/pnas.0406933101
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发表时间：
2004-10-26
影响因子：
11.1
通讯作者：
Taniguchi, T
中科院分区：
文献类型：
--
作者：
Honda, K;Yanai, H;Taniguchi, T
toll样受体（TLR）的激活是免疫的核心，其中TLR9亚家族成员TLR9和TLR7的激活通过MyD88接头蛋白导致I型ifn （ifn - α / β）的强烈诱导。然而，TLR信号“输入”如何通过MyD88加工“输出”IFN基因的诱导尚不清楚。在这里，我们证明转录因子IRF-7与MyD88相互作用，在细胞质中形成复合物。我们提供的证据表明，该复合物也涉及IRAK4和TRAF6，并为tlr9依赖性的IFN基因激活提供了基础。本研究中定义的复合体代表了信号接头和效应激酶分子与转录因子如何偶联调节细胞外信号的处理以唤起其在细胞中多种下游转录事件的一个例子。因此，我们认为这种分子复合物可能具有细胞质转导-转录处理器的功能。
Toll-like receptor (TLR) activation is central to immunity, wherein the activation of the TLR9 subfamily members TLR9 and TLR7 results in the robust induction of type I IFNs (IFN-alpha/beta) by means of the MyD88 adaptor protein. However, it remains unknown how the TLR signal "input" can be processed through MyD88 to "output" the induction of the IFN genes. Here, we demonstrate that the transcription factor IRF-7 interacts with MyD88 to form a complex in the cytoplasm. We provide evidence that this complex also involves IRAK4 and TRAF6 and provides the foundation for the TLR9-dependent activation of the IFN genes. The complex defined in this study represents an example of how the coupling of the signaling adaptor and effector kinase molecules together with the transcription factor regulate the processing of an extracellular signal to evoke its versatile downstream transcriptional events in a cell. Thus, we propose that this molecular complex may function as a cytoplasmic transductional-transcriptional processor.