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Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus

This study is designed to examine the cellular functions of human Fas-associated factor 1 (FAF1) containing multiple ubiquitin-related domains. Microarray analyses revealed that interferon-stimulated genes related to the antiviral response are significantly increased in FAF1-knockdown HeLa cells. Si...

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Autores principales: Song, Soonhwa, Lee, Jae-Jin, Kim, Hee-Jung, Lee, Jeong Yoon, Chang, Jun, Lee, Kong-Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800795/
https://www.ncbi.nlm.nih.gov/pubmed/26811330
http://dx.doi.org/10.1128/MCB.00744-15
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author Song, Soonhwa
Lee, Jae-Jin
Kim, Hee-Jung
Lee, Jeong Yoon
Chang, Jun
Lee, Kong-Joo
author_facet Song, Soonhwa
Lee, Jae-Jin
Kim, Hee-Jung
Lee, Jeong Yoon
Chang, Jun
Lee, Kong-Joo
author_sort Song, Soonhwa
collection PubMed
description This study is designed to examine the cellular functions of human Fas-associated factor 1 (FAF1) containing multiple ubiquitin-related domains. Microarray analyses revealed that interferon-stimulated genes related to the antiviral response are significantly increased in FAF1-knockdown HeLa cells. Silencing FAF1 enhanced the poly(I·C)- and respiratory syncytial virus (RSV)-induced production of type I interferons (IFNs), the target genes of interferon regulator factor 3 (IRF3). IRF3 is a key transcription factor in IFN-β signaling responsible for the host innate immune response. This study also found that FAF1 and IRF3 physically associate with IPO5/importin-β3 and that overexpression of FAF1 reduces the interaction between IRF3 and IPO5/importin-β3. These findings suggest that FAF1 negatively regulates IRF3-mediated IFN-β production and the antiviral innate immune response by regulating nuclear translocation of IRF3. We conclude that FAF1 plays a novel role in negatively regulating virus-induced IFN-β production and the antiviral response by inhibiting the translocation of active, phosphorylated IRF3 from the cytosol to the nucleus.
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spelling pubmed-48007952016-04-04 Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus Song, Soonhwa Lee, Jae-Jin Kim, Hee-Jung Lee, Jeong Yoon Chang, Jun Lee, Kong-Joo Mol Cell Biol Articles This study is designed to examine the cellular functions of human Fas-associated factor 1 (FAF1) containing multiple ubiquitin-related domains. Microarray analyses revealed that interferon-stimulated genes related to the antiviral response are significantly increased in FAF1-knockdown HeLa cells. Silencing FAF1 enhanced the poly(I·C)- and respiratory syncytial virus (RSV)-induced production of type I interferons (IFNs), the target genes of interferon regulator factor 3 (IRF3). IRF3 is a key transcription factor in IFN-β signaling responsible for the host innate immune response. This study also found that FAF1 and IRF3 physically associate with IPO5/importin-β3 and that overexpression of FAF1 reduces the interaction between IRF3 and IPO5/importin-β3. These findings suggest that FAF1 negatively regulates IRF3-mediated IFN-β production and the antiviral innate immune response by regulating nuclear translocation of IRF3. We conclude that FAF1 plays a novel role in negatively regulating virus-induced IFN-β production and the antiviral response by inhibiting the translocation of active, phosphorylated IRF3 from the cytosol to the nucleus. American Society for Microbiology 2016-03-18 /pmc/articles/PMC4800795/ /pubmed/26811330 http://dx.doi.org/10.1128/MCB.00744-15 Text en Copyright © 2016 Song et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Articles
Song, Soonhwa
Lee, Jae-Jin
Kim, Hee-Jung
Lee, Jeong Yoon
Chang, Jun
Lee, Kong-Joo
Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus
title Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus
title_full Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus
title_fullStr Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus
title_full_unstemmed Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus
title_short Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus
title_sort fas-associated factor 1 negatively regulates the antiviral immune response by inhibiting translocation of interferon regulatory factor 3 to the nucleus
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800795/
https://www.ncbi.nlm.nih.gov/pubmed/26811330
http://dx.doi.org/10.1128/MCB.00744-15
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