title: SIRT2 regulates NF-κB dependent gene expression through deacetylation of p65 Lys310.
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.
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstraße 190, 8057 Zurich, Switzerland.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Rothgiesser
authors.forename: Süheda
authors.initials: S
authors.lastname: Erener
authors.forename: Susanne
authors.initials: S
authors.lastname: Waibel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000918:Antibody Specificity / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015203:Reproducibility of Results; D056564:Sirtuin 1 / Q000172:deficiency / Q000378:metabolism; D056565:Sirtuin 2 / Q000172:deficiency / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C470545:Sirt1 protein, mouse; C418743:Sirt2 protein, mouse; D056564:Sirtuin 1; D056565:Sirtuin 2; D008239:Lysine