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Publication : Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling.

First Author  Honda K Year  2004
Journal  Proc Natl Acad Sci U S A Volume  101
Issue  43 Pages  15416-21
PubMed ID  15492225 Mgi Jnum  J:93531
Mgi Id  MGI:3057241 Doi  10.1073/pnas.0406933101
Citation  Honda K, et al. (2004) Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc Natl Acad Sci U S A 101(43):15416-21
abstractText  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.
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