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KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly
Despite progress in understanding how virus-induced, NF-κB-dependent pro-inflammatory cytokines are regulated, there are still factors and mechanisms that remain to be explored. We aimed to uncover the relationship between KRAB-zinc finger protein ZNF268a and NF-κB-mediated cytokine production in re...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953056/ https://www.ncbi.nlm.nih.gov/pubmed/31835635 http://dx.doi.org/10.3390/cells8121604 |
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author | Liu, Yi Yin, Wei Wang, Jingwen Lei, Yucong Sun, Guihong Li, Wenxin Huang, Zan Guo, Mingxiong |
author_facet | Liu, Yi Yin, Wei Wang, Jingwen Lei, Yucong Sun, Guihong Li, Wenxin Huang, Zan Guo, Mingxiong |
author_sort | Liu, Yi |
collection | PubMed |
description | Despite progress in understanding how virus-induced, NF-κB-dependent pro-inflammatory cytokines are regulated, there are still factors and mechanisms that remain to be explored. We aimed to uncover the relationship between KRAB-zinc finger protein ZNF268a and NF-κB-mediated cytokine production in response to viral infection. To this end, we established a ZNF268a-knockout cell line using a pair of sgRNAs that simultaneously target exon 3 in the coding sequence of the ZNF268 gene in HEK293T. HEK293T cells lacking ZNF268a showed less cytokine expression at the transcription and protein levels in response to Sendai virus/vesicular stomatitis virus (SeV/VSV) infection than wild-type cells. Consistent with HEK293T, knock-down of ZNF268a by siRNAs in THP-1 cells significantly dampened the inflammatory response. Mechanistically, ZNF268a facilitated NF-κB activation by targeting IKKα, helping to maintain the IKK signaling complex and thus enabling proper p65 phosphorylation and nuclear translocation. Taken together, our data suggest that ZNF268a plays a positive role in the regulation of virus-induced pro-inflammatory cytokine production. By interacting with IKKα, ZNF268a promotes NF-κB signal transduction upon viral infection by helping to maintain the association between IKK complex subunits. |
format | Online Article Text |
id | pubmed-6953056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69530562020-01-23 KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly Liu, Yi Yin, Wei Wang, Jingwen Lei, Yucong Sun, Guihong Li, Wenxin Huang, Zan Guo, Mingxiong Cells Article Despite progress in understanding how virus-induced, NF-κB-dependent pro-inflammatory cytokines are regulated, there are still factors and mechanisms that remain to be explored. We aimed to uncover the relationship between KRAB-zinc finger protein ZNF268a and NF-κB-mediated cytokine production in response to viral infection. To this end, we established a ZNF268a-knockout cell line using a pair of sgRNAs that simultaneously target exon 3 in the coding sequence of the ZNF268 gene in HEK293T. HEK293T cells lacking ZNF268a showed less cytokine expression at the transcription and protein levels in response to Sendai virus/vesicular stomatitis virus (SeV/VSV) infection than wild-type cells. Consistent with HEK293T, knock-down of ZNF268a by siRNAs in THP-1 cells significantly dampened the inflammatory response. Mechanistically, ZNF268a facilitated NF-κB activation by targeting IKKα, helping to maintain the IKK signaling complex and thus enabling proper p65 phosphorylation and nuclear translocation. Taken together, our data suggest that ZNF268a plays a positive role in the regulation of virus-induced pro-inflammatory cytokine production. By interacting with IKKα, ZNF268a promotes NF-κB signal transduction upon viral infection by helping to maintain the association between IKK complex subunits. MDPI 2019-12-10 /pmc/articles/PMC6953056/ /pubmed/31835635 http://dx.doi.org/10.3390/cells8121604 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Yi Yin, Wei Wang, Jingwen Lei, Yucong Sun, Guihong Li, Wenxin Huang, Zan Guo, Mingxiong KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly |
title | KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly |
title_full | KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly |
title_fullStr | KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly |
title_full_unstemmed | KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly |
title_short | KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly |
title_sort | krab-zinc finger protein znf268a deficiency attenuates the virus-induced pro-inflammatory response by preventing ikk complex assembly |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953056/ https://www.ncbi.nlm.nih.gov/pubmed/31835635 http://dx.doi.org/10.3390/cells8121604 |
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