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Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1
BACKGROUND: The NAD-dependent protein deacetylase SIRT1 has a wide range of different targets, which may be regulated either directly through deacetylation and thus potentially altering their activity or localization or indirectly by deacetylation of histones, which in turn alters their transcriptio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727996/ https://www.ncbi.nlm.nih.gov/pubmed/23870485 http://dx.doi.org/10.1186/1868-7083-5-11 |
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author | Katto, Judith Engel, Nicole Abbas, Wasim Herbein, Georges Mahlknecht, Ulrich |
author_facet | Katto, Judith Engel, Nicole Abbas, Wasim Herbein, Georges Mahlknecht, Ulrich |
author_sort | Katto, Judith |
collection | PubMed |
description | BACKGROUND: The NAD-dependent protein deacetylase SIRT1 has a wide range of different targets, which may be regulated either directly through deacetylation and thus potentially altering their activity or localization or indirectly by deacetylation of histones, which in turn alters their transcription rate and availability. SIRT1 is therefore involved in the regulation of many different and fundamental cellular processes such as apoptosis, metabolism, differentiation and cell cycle arrest. It is also involved in the regulation of resistance of cells against oxidative stress and longevity under conditions of caloric restriction. Even though the targets and role of SIRT1 have been studied quite intensively, only little is known about the mechanisms affecting SIRT1 transcriptional regulation. The nuclear factor NFκB is a well-studied and widely known transcription factor, which is involved in the regulation of many important cellular activities. The regulation of NFκB by SIRT1 has been reported recently, but it is, however, still unknown whether a feedback mechanism affects the regulation of SIRT1 too, particularly in view of the fact that putative NFκB binding sites within the SIRT1 promoter suggest just that. RESULTS: In the study presented herein we show that there is activation of the SIRT1 promoter by overexpression of different NFκB subunits. Direct binding of NFκB to the SIRT1 promoter can be demonstrated by an electrophoretic mobility shift assay. Further investigations indicated enhanced expression of SIRT1 on the mRNA levels in cells overexpressing NFκB. A functional assay showed that acetylation of one of the main target proteins of SIRT1 is reduced in these cells. CONCLUSIONS: These finding together indicate SIRT1 expression to be regulated in a positive feedback loop by NFκB. The putative binding sites for NFκB found within the SIRT1 promoter appears to be functional and several NFκB subunits are able to enhance the expression of SIRT1 if they are overexpressed. |
format | Online Article Text |
id | pubmed-3727996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37279962013-07-31 Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1 Katto, Judith Engel, Nicole Abbas, Wasim Herbein, Georges Mahlknecht, Ulrich Clin Epigenetics Research BACKGROUND: The NAD-dependent protein deacetylase SIRT1 has a wide range of different targets, which may be regulated either directly through deacetylation and thus potentially altering their activity or localization or indirectly by deacetylation of histones, which in turn alters their transcription rate and availability. SIRT1 is therefore involved in the regulation of many different and fundamental cellular processes such as apoptosis, metabolism, differentiation and cell cycle arrest. It is also involved in the regulation of resistance of cells against oxidative stress and longevity under conditions of caloric restriction. Even though the targets and role of SIRT1 have been studied quite intensively, only little is known about the mechanisms affecting SIRT1 transcriptional regulation. The nuclear factor NFκB is a well-studied and widely known transcription factor, which is involved in the regulation of many important cellular activities. The regulation of NFκB by SIRT1 has been reported recently, but it is, however, still unknown whether a feedback mechanism affects the regulation of SIRT1 too, particularly in view of the fact that putative NFκB binding sites within the SIRT1 promoter suggest just that. RESULTS: In the study presented herein we show that there is activation of the SIRT1 promoter by overexpression of different NFκB subunits. Direct binding of NFκB to the SIRT1 promoter can be demonstrated by an electrophoretic mobility shift assay. Further investigations indicated enhanced expression of SIRT1 on the mRNA levels in cells overexpressing NFκB. A functional assay showed that acetylation of one of the main target proteins of SIRT1 is reduced in these cells. CONCLUSIONS: These finding together indicate SIRT1 expression to be regulated in a positive feedback loop by NFκB. The putative binding sites for NFκB found within the SIRT1 promoter appears to be functional and several NFκB subunits are able to enhance the expression of SIRT1 if they are overexpressed. BioMed Central 2013-07-19 /pmc/articles/PMC3727996/ /pubmed/23870485 http://dx.doi.org/10.1186/1868-7083-5-11 Text en Copyright © 2013 Katto et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Katto, Judith Engel, Nicole Abbas, Wasim Herbein, Georges Mahlknecht, Ulrich Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1 |
title | Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1 |
title_full | Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1 |
title_fullStr | Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1 |
title_full_unstemmed | Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1 |
title_short | Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1 |
title_sort | transcription factor nfκb regulates the expression of the histone deacetylase sirt1 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727996/ https://www.ncbi.nlm.nih.gov/pubmed/23870485 http://dx.doi.org/10.1186/1868-7083-5-11 |
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