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Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3

As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially in...

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Autores principales: Homma, Takujiro, Ishibashi, Daisuke, Nakagaki, Takehiro, Fuse, Takayuki, Sano, Kazunori, Satoh, Katsuya, Atarashi, Ryuichiro, Nishida, Noriyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126003/
https://www.ncbi.nlm.nih.gov/pubmed/25103253
http://dx.doi.org/10.1038/srep06006
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author Homma, Takujiro
Ishibashi, Daisuke
Nakagaki, Takehiro
Fuse, Takayuki
Sano, Kazunori
Satoh, Katsuya
Atarashi, Ryuichiro
Nishida, Noriyuki
author_facet Homma, Takujiro
Ishibashi, Daisuke
Nakagaki, Takehiro
Fuse, Takayuki
Sano, Kazunori
Satoh, Katsuya
Atarashi, Ryuichiro
Nishida, Noriyuki
author_sort Homma, Takujiro
collection PubMed
description As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions. Here, we found that stable infection of prion suppressed IRF-3 gene-expression. The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription. We further investigated promoter activity of 5′- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity. Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region. In addition, overexpression of Oct-1 increased the promoter activity of IRF-3. Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups. Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3.
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spelling pubmed-41260032014-08-14 Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3 Homma, Takujiro Ishibashi, Daisuke Nakagaki, Takehiro Fuse, Takayuki Sano, Kazunori Satoh, Katsuya Atarashi, Ryuichiro Nishida, Noriyuki Sci Rep Article As a prompt response against invasion of various viruses, interferon regulatory factor-3 (IRF-3) is initially phosphorylated to become activated and upregulates mainly Type I Interferons (IFN-I) in most cell types. We previously reported that IRF-3-dependent host innate immune responses partially interfere in infection of prions. Here, we found that stable infection of prion suppressed IRF-3 gene-expression. The decreased promoter activity of IRF-3 was significantly restored along with treatment of anti-prion drugs in the prion-infected cells, suggesting that infection of prion directly influence the regulation of IRF-3 transcription. We further investigated promoter activity of 5′- flanking region of murine IRF-3 using a luciferase reporter system and found that the nucleotides -119 to -1 were indispensable for the promoter activity. Within this region, mutations in the Oct-1 binding site significantly reduced the promoter activity and chromatin immunoprecipitation (ChIP) assay revealed that Oct-1 indeed binds to the region. In addition, overexpression of Oct-1 increased the promoter activity of IRF-3. Intriguingly, Oct-1 protein was significantly reduced in prion-infected cells and mice brains compared with uninfected groups. Taken together, we concluded that prion infection could interfere in the function of Oct-1, resulting in the down-regulation of IRF-3. Nature Publishing Group 2014-08-08 /pmc/articles/PMC4126003/ /pubmed/25103253 http://dx.doi.org/10.1038/srep06006 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Article
Homma, Takujiro
Ishibashi, Daisuke
Nakagaki, Takehiro
Fuse, Takayuki
Sano, Kazunori
Satoh, Katsuya
Atarashi, Ryuichiro
Nishida, Noriyuki
Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3
title Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3
title_full Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3
title_fullStr Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3
title_full_unstemmed Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3
title_short Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3
title_sort persistent prion infection disturbs the function of oct-1, resulting in the down-regulation of murine interferon regulatory factor-3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126003/
https://www.ncbi.nlm.nih.gov/pubmed/25103253
http://dx.doi.org/10.1038/srep06006
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