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

Kenya Honda, Hideyuki Yanai, Tatsuaki Mizutani, Hideo Negishi, Naoya Shimada, Nobutaka Suzuki, Yusuke Ohba, Akinori Takaoka, Wen Chen Yeh, Tadatsugu Taniguchi

Research output: Contribution to journalArticle

391 Citations (Scopus)

Abstract

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-α/β) 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.

Original languageEnglish
Pages (from-to)15416-15421
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number43
DOIs
Publication statusPublished - 2004 Oct 26
Externally publishedYes

ASJC Scopus subject areas

  • General

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