Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase

EMBO J. 2004 Jun 16;23(12):2369-80. doi: 10.1038/sj.emboj.7600244. Epub 2004 May 20.


NF-kappaB is responsible for upregulating gene products that control cell survival. In this study, we demonstrate that SIRT1, a nicotinamide adenosine dinucleotide-dependent histone deacetylase, regulates the transcriptional activity of NF-kappaB. SIRT1, the mammalian ortholog of the yeast SIR2 (Silencing Information Regulator) and a member of the Sirtuin family, has been implicated in modulating transcriptional silencing and cell survival. SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310. Treatment of cells with resveratrol, a small-molecule agonist of Sirtuin activity, potentiates chromatin-associated SIRT1 protein on the cIAP-2 promoter region, an effect that correlates with a loss of NF-kappaB-regulated gene expression and sensitization of cells to TNFalpha-induced apoptosis. While SIRT1 is capable of protecting cells from p53-induced apoptosis, our work provides evidence that SIRT1 activity augments apoptosis in response to TNFalpha by the ability of the deacetylase to inhibit the transactivation potential of the RelA/p65 protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Survival / physiology*
  • DNA Primers
  • Histone Deacetylases / physiology*
  • Humans
  • NF-kappa B / physiology*
  • Resveratrol
  • Sirtuin 1
  • Sirtuins / physiology*
  • Stilbenes / pharmacology
  • Transcription, Genetic / physiology*


  • DNA Primers
  • NF-kappa B
  • Stilbenes
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins
  • Histone Deacetylases
  • Resveratrol