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
Hauptverfasser: Rothgiesser, Karin M, Erener, Süheda, Waibel, Susanne, Lüscher, Bernhard, Hottiger, Michael O
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container_end_page 4258
container_issue 24
container_start_page 4251
container_title Journal of cell science
container_volume 123
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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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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