Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Open accessAbstract
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.
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SIRT1 interacts with RelA/p65 protein in the NF-κB complex, deacetylates lysine 310, and potentiates the transactivation capacity of the NF-κB complex.
“A similar trend is observed in the interaction of SIRT1 with RelA/p65 protein in the NF-κB complex which deacetylates lysine 310 and potentiates the transactivation capacity of the NF-κB complex [197].”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [197]
Corepressor complexes that remove acetyl groups from Lys310 reduce p65 activity.
“In contrast, deacetylation at Lys310 by corepressor complexes inhibits p65 activity [56, 57].”
From Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes (2013) · cites this paper as [57]
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References 53 · Cited by 2,750
- Authors
- Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W.
- Affiliations
- University of Virginia (US)
- VA Pittsburgh Healthcare System (US)
- Corresponding author
- Mayo, Marty W
- Venue
- The EMBO Journal
- Published
- 2004-05-20
- Volume
- 23
- Issue
- 12
- Pages
- 2369-2380
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC423286
- OpenAlex
- W2140925956
- Cited by
- 2,750
- References
- 53
- Citations by year
- 2026: 118 · 2025: 112 · 2024: 127 · 2023: 118 · 2022: 156 · 2021: 183 · 2020: 146 · 2019: 140 · 2018: 139 · 2017: 140 · 2016: 137 · 2015: 164 · 2014: 145 · 2013: 168 · 2012: 146
- FWCI
- 26.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- University of Bern
- National Institutes of Health (5k01ca078595-04)
- University of North Carolina at Chapel Hill
- National Cancer Institute (K01CA78595, R01CA104397, R01CA095644, CA-110552-01, F32CA110552)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- SIRT1, NF-κB, RelA/p65, histone deacetylase, transcriptional regulation, cell survival, resveratrol, cIAP2, TNFα-induced apoptosis, sirtuins, chromatin
- MeSH terms
- Resveratrol, Base Sequence, Cell Survival, Histone Deacetylases, Humans, Stilbenes, Transcription, Genetic, NF-kappa B, DNA Primers, Sirtuins, Cell Line, Tumor, Sirtuin 1
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