SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310
NF-κB regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. In this study, we identified SIRT2 as a deacetylase of the transcription factor p65. SIRT2 is a member of the family of sirt...
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Veröffentlicht in: | Journal of cell science 2010-12, Vol.123 (24), p.4251-4258 |
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creator | Rothgiesser, Karin M Erener, Süheda Waibel, Susanne Lüscher, Bernhard Hottiger, Michael O |
description | NF-κB regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. In this study, we identified SIRT2 as a deacetylase of the transcription factor p65. SIRT2 is a member of the family of sirtuins, which are NAD⁺-dependent deacetylases involved in several cellular processes. SIRT2 interacts with p65 in the cytoplasm and deacetylates p65 in vitro and in vivo at Lys310. Moreover, p65 is hyperacetylated at Lys310 in Sirt2⁻/⁻ cells after TNFα stimulation, which results in the increase in expression of a subset of p65 acetylation-dependent target genes. Our work provides evidence that p65 is deacetylated by SIRT2 in the cytoplasm to regulate the expression of specific NF-κB-dependent genes. |
doi_str_mv | 10.1242/jcs.073783 |
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In this study, we identified SIRT2 as a deacetylase of the transcription factor p65. SIRT2 is a member of the family of sirtuins, which are NAD⁺-dependent deacetylases involved in several cellular processes. SIRT2 interacts with p65 in the cytoplasm and deacetylates p65 in vitro and in vivo at Lys310. Moreover, p65 is hyperacetylated at Lys310 in Sirt2⁻/⁻ cells after TNFα stimulation, which results in the increase in expression of a subset of p65 acetylation-dependent target genes. 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In this study, we identified SIRT2 as a deacetylase of the transcription factor p65. SIRT2 is a member of the family of sirtuins, which are NAD⁺-dependent deacetylases involved in several cellular processes. SIRT2 interacts with p65 in the cytoplasm and deacetylates p65 in vitro and in vivo at Lys310. Moreover, p65 is hyperacetylated at Lys310 in Sirt2⁻/⁻ cells after TNFα stimulation, which results in the increase in expression of a subset of p65 acetylation-dependent target genes. Our work provides evidence that p65 is deacetylated by SIRT2 in the cytoplasm to regulate the expression of specific NF-κB-dependent genes.</description><subject>Acetylation - drug effects</subject><subject>Animals</subject><subject>Antibody Specificity - drug effects</subject><subject>Apoptosis - drug effects</subject><subject>Cell Nucleus - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Embryo, Mammalian - cytology</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Expression Regulation - drug effects</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Lysine - metabolism</subject><subject>Mice</subject><subject>NIH 3T3 Cells</subject><subject>Protein Binding - drug effects</subject><subject>Protein Transport - drug effects</subject><subject>Reproducibility of Results</subject><subject>Sirtuin 1 - deficiency</subject><subject>Sirtuin 1 - metabolism</subject><subject>Sirtuin 2 - deficiency</subject><subject>Sirtuin 2 - metabolism</subject><subject>Transcription Factor RelA - metabolism</subject><subject>Transcriptional Activation - drug effects</subject><subject>Transcriptional Activation - genetics</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0M9Kw0AQBvBFFK1_Lj6A5iYIqTO72Wz2qMVqoSjY9rxskklbaZO4m4B9NR_CZzKl1aungeE3H8PH2CVCH3nE794z3wclVCIOWA8jpUKNQh2yHgDHUEshTtip9-8AoLhWx-yEIyQYR7rHppPR25QHjubtyjbkg5dh-P31EOZUU5lT2QRzKimgz9qR98uqDJqFq9r5IsjJZtRsuqvttiqCOpbBeOMFwjk7KuzK08V-nrHZ8HE6eA7Hr0-jwf04zLpnmxBRyii1lqdZIkUsoiJKRYEEGfJckpKYgIpTIblKCpHrLI07lmOulCwoFeKM3exya1d9tOQbs176jFYrW1LVeqNBoQSE-F-ZoNSxUMg7ebuTmau8d1SY2i3X1m0MgtnWbbq6za7uDl_tY9t0Tfkf_e23A9c7UNjK2LlbejObcEABqDHWIMUPUwmCiw</recordid><startdate>20101215</startdate><enddate>20101215</enddate><creator>Rothgiesser, Karin M</creator><creator>Erener, Süheda</creator><creator>Waibel, Susanne</creator><creator>Lüscher, Bernhard</creator><creator>Hottiger, Michael O</creator><general>The Company of Biologists Limited</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20101215</creationdate><title>SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310</title><author>Rothgiesser, Karin M ; Erener, Süheda ; Waibel, Susanne ; Lüscher, Bernhard ; Hottiger, Michael O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-11554baa2bc853634f4b3f1e0c12d5e7518076b35278f3d9cb6536d1d775feb33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acetylation - drug effects</topic><topic>Animals</topic><topic>Antibody Specificity - drug effects</topic><topic>Apoptosis - drug effects</topic><topic>Cell Nucleus - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Embryo, Mammalian - cytology</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Gene Expression Regulation - drug effects</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Lysine - metabolism</topic><topic>Mice</topic><topic>NIH 3T3 Cells</topic><topic>Protein Binding - drug effects</topic><topic>Protein Transport - drug effects</topic><topic>Reproducibility of Results</topic><topic>Sirtuin 1 - deficiency</topic><topic>Sirtuin 1 - metabolism</topic><topic>Sirtuin 2 - deficiency</topic><topic>Sirtuin 2 - metabolism</topic><topic>Transcription Factor RelA - metabolism</topic><topic>Transcriptional Activation - drug effects</topic><topic>Transcriptional Activation - genetics</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rothgiesser, Karin M</creatorcontrib><creatorcontrib>Erener, Süheda</creatorcontrib><creatorcontrib>Waibel, Susanne</creatorcontrib><creatorcontrib>Lüscher, Bernhard</creatorcontrib><creatorcontrib>Hottiger, Michael O</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rothgiesser, Karin M</au><au>Erener, Süheda</au><au>Waibel, Susanne</au><au>Lüscher, Bernhard</au><au>Hottiger, Michael O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2010-12-15</date><risdate>2010</risdate><volume>123</volume><issue>24</issue><spage>4251</spage><epage>4258</epage><pages>4251-4258</pages><issn>0021-9533</issn><eissn>1477-9137</eissn><abstract>NF-κB regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. 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subjects | Acetylation - drug effects Animals Antibody Specificity - drug effects Apoptosis - drug effects Cell Nucleus - drug effects Cell Nucleus - metabolism Embryo, Mammalian - cytology Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism Gene Expression Regulation - drug effects HeLa Cells Humans Kinetics Lysine - metabolism Mice NIH 3T3 Cells Protein Binding - drug effects Protein Transport - drug effects Reproducibility of Results Sirtuin 1 - deficiency Sirtuin 1 - metabolism Sirtuin 2 - deficiency Sirtuin 2 - metabolism Transcription Factor RelA - metabolism Transcriptional Activation - drug effects Transcriptional Activation - genetics Tumor Necrosis Factor-alpha - pharmacology |
title | SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310 |
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