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SIRT2 regulates NF-κB dependent gene expression through deacetylation of p65 Lys310

Rothgiesser, Karin M., Erener, Süheda, Waibel, Susanne, Lüscher, Bernhard, Hottiger, Michael O.·2010·Journal of Cell Science

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.

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Crossref · 10.1242/jcs.073783

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  • SIRT2 and SIRT6 may down-regulate the inflammatory response through deacetylation of NF-kB subunits and transcriptional repression of their target genes.

    “SIRT2 and SIRT6 may also down-regulate the inflammatory response through deacetylation of NF-kB subunits and transcriptional repression of their target genes”

    From The Hallmarks of Aging (2013) · cites this paper as Rothgiesser et al., 2010

    The Abstract and the section on SIRT2-dependent gene expression report that SIRT2 deacetylates the NF-κB subunit p65 and limits expression of a subset of its target genes. The Discussion explicitly says SIRT6 does not deacetylate p65; it describes SIRT6 as attenuating NF-κB signaling by deacetylating histone H3K9 instead. Thus the proposed mechanism is supported for SIRT2, not SIRT6. (LLM, conf=0.90)

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Research works printed but not linked: 35

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Metadata

Authors
Rothgiesser, K. M., Erener, S., Waibel, S., Lüscher, B., & Hottiger, M. O.
Affiliations
  • Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstraße 190, 8057 Zurich, Switzerland
  • Institut für Biochemie und Molekularbiologie, Medical School, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany
Venue
Journal of Cell Science
Published
2010-12-15
Volume
123
Issue
24
Pages
4251-4258
ISSN
  • 1477-9137
  • 0021-9533
Cited by
345
References
5
Language
en

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