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Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila
The activation of several transcription factors is required for the elimination of infectious pathogens via the innate immune response. The transcription factors NF-κB, AP-1, and STAT play major roles in the synthesis of immune effector molecules during innate immune responses. However, the fact tha...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964775/ https://www.ncbi.nlm.nih.gov/pubmed/17803358 http://dx.doi.org/10.1371/journal.pbio.0050238 |
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author | Kim, Lark Kyun Choi, Un Yung Cho, Hwan Sung Lee, Jung Seon Lee, Wook-bin Kim, Jihyun Jeong, Kyoungsuk Shim, Jaewon Kim-Ha, Jeongsil Kim, Young-Joon |
author_facet | Kim, Lark Kyun Choi, Un Yung Cho, Hwan Sung Lee, Jung Seon Lee, Wook-bin Kim, Jihyun Jeong, Kyoungsuk Shim, Jaewon Kim-Ha, Jeongsil Kim, Young-Joon |
author_sort | Kim, Lark Kyun |
collection | PubMed |
description | The activation of several transcription factors is required for the elimination of infectious pathogens via the innate immune response. The transcription factors NF-κB, AP-1, and STAT play major roles in the synthesis of immune effector molecules during innate immune responses. However, the fact that these immune responses can have cytotoxic effects requires their tight regulation to achieve restricted and transient activation, and mis-regulation of the damping process has pathological consequences. Here we show that AP-1 and STAT are themselves the major inhibitors responsible for damping NF-κB–mediated transcriptional activation during the innate immune response in Drosophila. As the levels of dAP-1 and Stat92E increase due to continuous immune signaling, they play a repressive role by forming a repressosome complex with the Drosophila HMG protein, Dsp1. The dAP-1–, Stat92E-, and Dsp1-containing complexes replace Relish at the promoters of diverse immune effector genes by binding to evolutionarily conserved cis-elements, and they recruit histone deacetylase to inhibit transcription. Reduction by mutation of dAP-1, Stat92E, or Dsp1 results in hyperactivation of Relish target genes and reduces the viability of bacterially infected flies despite more efficient pathogen clearance. These defects are rescued by reducing the Relish copy number, thus confirming that mis-regulation of Relish, not inadequate activation of dAP-1, Stat92E, or Dsp1 target genes, is responsible for the reduced survival of the mutants. We conclude that an inhibitory effect of AP-1 and STAT on NF-κB is required for properly balanced immune responses and appears to be evolutionarily conserved. |
format | Text |
id | pubmed-1964775 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-19647752007-09-05 Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila Kim, Lark Kyun Choi, Un Yung Cho, Hwan Sung Lee, Jung Seon Lee, Wook-bin Kim, Jihyun Jeong, Kyoungsuk Shim, Jaewon Kim-Ha, Jeongsil Kim, Young-Joon PLoS Biol Research Article The activation of several transcription factors is required for the elimination of infectious pathogens via the innate immune response. The transcription factors NF-κB, AP-1, and STAT play major roles in the synthesis of immune effector molecules during innate immune responses. However, the fact that these immune responses can have cytotoxic effects requires their tight regulation to achieve restricted and transient activation, and mis-regulation of the damping process has pathological consequences. Here we show that AP-1 and STAT are themselves the major inhibitors responsible for damping NF-κB–mediated transcriptional activation during the innate immune response in Drosophila. As the levels of dAP-1 and Stat92E increase due to continuous immune signaling, they play a repressive role by forming a repressosome complex with the Drosophila HMG protein, Dsp1. The dAP-1–, Stat92E-, and Dsp1-containing complexes replace Relish at the promoters of diverse immune effector genes by binding to evolutionarily conserved cis-elements, and they recruit histone deacetylase to inhibit transcription. Reduction by mutation of dAP-1, Stat92E, or Dsp1 results in hyperactivation of Relish target genes and reduces the viability of bacterially infected flies despite more efficient pathogen clearance. These defects are rescued by reducing the Relish copy number, thus confirming that mis-regulation of Relish, not inadequate activation of dAP-1, Stat92E, or Dsp1 target genes, is responsible for the reduced survival of the mutants. We conclude that an inhibitory effect of AP-1 and STAT on NF-κB is required for properly balanced immune responses and appears to be evolutionarily conserved. Public Library of Science 2007-09 2007-09-04 /pmc/articles/PMC1964775/ /pubmed/17803358 http://dx.doi.org/10.1371/journal.pbio.0050238 Text en © 2007 Kim et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kim, Lark Kyun Choi, Un Yung Cho, Hwan Sung Lee, Jung Seon Lee, Wook-bin Kim, Jihyun Jeong, Kyoungsuk Shim, Jaewon Kim-Ha, Jeongsil Kim, Young-Joon Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila |
title | Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila
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title_full | Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila
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title_fullStr | Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila
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title_full_unstemmed | Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila
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title_short | Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila
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title_sort | down-regulation of nf-κb target genes by the ap-1 and stat complex during the innate immune response in drosophila |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1964775/ https://www.ncbi.nlm.nih.gov/pubmed/17803358 http://dx.doi.org/10.1371/journal.pbio.0050238 |
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