SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310.
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Rothgiesser KM, Erener S, Waibel S, Luscher B, Hottiger MO
SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310.
J Cell Sci. 2010 Dec 15;123(Pt 24):4251-8. doi: 10.1242/jcs.073783. Epub 2010 Nov 16.
- PubMed ID
- 21081649 [ View in PubMed]
- Abstract
NF-kappaB 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 TNFalpha 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-kappaB-dependent genes.