TY - JOUR
T1 - Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling
AU - Honda, Kenya
AU - Yanai, Hideyuki
AU - Mizutani, Tatsuaki
AU - Negishi, Hideo
AU - Shimada, Naoya
AU - Suzuki, Nobutaka
AU - Ohba, Yusuke
AU - Takaoka, Akinori
AU - Yeh, Wen Chen
AU - Taniguchi, Tadatsugu
PY - 2004/10/26
Y1 - 2004/10/26
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0406933101
DO - 10.1073/pnas.0406933101
M3 - Article
C2 - 15492225
AN - SCOPUS:7444250116
VL - 101
SP - 15416
EP - 15421
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 43
ER -