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. 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation / drug effects
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Animals
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Antibody Specificity / drug effects
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Apoptosis / drug effects
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Embryo, Mammalian / cytology
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Gene Expression Regulation* / drug effects
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HeLa Cells
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Humans
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Kinetics
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Lysine / metabolism*
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Mice
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NIH 3T3 Cells
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Protein Binding / drug effects
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Protein Transport / drug effects
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Reproducibility of Results
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Sirtuin 1 / deficiency
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Sirtuin 1 / metabolism
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Sirtuin 2 / deficiency
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Sirtuin 2 / metabolism*
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Transcription Factor RelA / metabolism*
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Transcriptional Activation / drug effects
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Transcriptional Activation / genetics
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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Sirt1 protein, mouse
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Sirt2 protein, mouse
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Sirtuin 1
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Sirtuin 2
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Lysine