2007 Fiscal Year Final Research Report Summary
Analyses on Mechanisms for Multistep Transcriptional Regulation via Inducible Factors
| Project/Area Number |
18370056
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
MUTA Tatsushi Tohoku University, Tohoku University, Grad, Sch. Life Sci., Professor (60222337)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Keywords | regulation of expression / gene / infectious disease / immunology / signal transduction / transcriptional regulation / innate immunity / induction of expression |
|---|
| Research Abstract |
IκB-ζ, which was discovered by the head investigator, is a key molecule playing dual roles in regulation of inflammatory reactions. IκB-ζ is induced by various microbial substances stimulating the innate immune system and is essential for transcription of secondary response genes such as interleukin (IL)-6, IL-12, and the transcription factor C/EBP-δ and suppresses those of primary response genes represented by tumor necrosis factor (TNF)-α. In the present study, we investigated mechanisms for transcriptional regulation by IκB-ζ. We found that both an NF-κB binding site and a C/EBP binding site in the promoter region are essential for the transcriptional activation by IκB-ζ in the human β-defensin 2 and neutrophil gelatinase-associated lipocalin genes. On the other hand, IκB-ζ inhibited transcription of a promoter harboring canonical NF-κB binding sites. These results indicated that IκB-ζ induced on stimulation forms a complex with NF-κB and binds to the promoters harboring an NF-κB binding site and a C/EBP sites, where it activates transcription. Induction of IκB-ζ is induced by IL-1β stimulation as well as LPS, but not by TNF-α. We have analyzed mechanisms for IκB-ζ induction and have shown that IκB-ζ mRNA is specifically stabilized upon LPS/IL-1β stimulation. In the present study, we searched for an element in the IκB-ζ mRNA that is essential for the post-transcriptional regulation, and found that a 165-nucleotide sequence in the 3'-untranslated region is essential and sufficient for the regulation. We furthermore examined induction of IκB-ζ in B cells and found that it is induced upon stimulation of B cell antigen receptor. We also found that the induction was inhibited by co-stimulation of the inhibitory Fc receptor. These results strongly suggest that IκB-ζ plays a critical role in the adaptive immune system.
|
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Ifi202, an IFN-inducible candidate gene for lupus susceptibility in NZB/W Fl mice, is a positive regulator for NF-κB activation in dendritic cells2007
Author(s)
Yamauchi, M., Hashimoto, M., Ichiyama, K, Yoshida, R., Hanada, T., Muta. T., Komune, S., Kobayashi, T., and Yoshimura, A.
-
Journal Title
Int. Immunol 19
Pages: 935-942
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
[Journal Article] A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy2006
Author(s)
Hidaka, F., Matsuo, S., Muta. T., Takeshige, K., Mizukami, T., and Nunoi, H.
-
Journal Title
Clin. Immunol. 119
Pages: 188-194
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Transcriptional Regulation of Innate Immune Responses by I_kB-ζ, a Nuclear I_kB Protein2007
Author(s)
Muta. T., Matsuo, S., Watanabe, S., and Takeshige, K
Organizer
19^<th> FAOBMB Conference, Symposium "Innate Immunity", Oral Presentation
Place of Presentation
Poster Presentation May 28, 2007, Seoul, South Korea.
Year and Date
2007-05-27
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
