The DOI matches its Crossref record; 73 of the 77 references it cites were found in a registry or an index.
NF-κB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK
Open accessAbstract
Constitutively activated NF-kappaB occurs in many inflammatory and tumor tissues. Does it interfere with anti-inflammatory or anti-tumor signaling pathway? Here, we report that NF-kappaB p65 subunit repressed the Nrf2-antioxidant response element (ARE) pathway at transcriptional level. In the cells where NF-kappaB and Nrf2 were simultaneously activated, p65 unidirectionally antagonized the transcriptional activity of Nrf2. In the p65-overexpressing cells, the ARE-dependent expression of heme oxygenase-1 was strongly suppressed. However, p65 inhibited the ARE-driven gene transcription in a way that was independent of its own transcriptional activity. Two mechanisms were found to coordinate the p65-mediated repression of ARE: (1) p65 selectively deprives CREB binding protein (CBP) from Nrf2 by competitive interaction with the CH1-KIX domain of CBP, which results in inactivation of Nrf2. The inactivation depends on PKA catalytic subunit-mediated phosphorylation of p65 at S276. (2) p65 promotes recruitment of histone deacetylase 3 (HDAC3), the corepressor, to ARE by facilitating the interaction of HDAC3 with either CBP or MafK, leading to local histone hypoacetylation. This investigation revealed the participation of NF-kappaB p65 in the negative regulation of Nrf2-ARE signaling, and might provide a new insight into a possible role of NF-kappaB in suppressing the expression of anti-inflammatory or anti-tumor genes.
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“In addition, decreased levels of Nrf2, a transcription factor negatively regulated by NF-κB (Liu et al., 2008) that is involved in antioxidants response mechanisms (Nair et al., 2008), have been reported in the brains of AD patients (Ramsey et al., 2007).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Liu et al., 2008
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1 retracted
Cytokines suppress adipogenesis and PPAR-γ function through the TAK1/TAB1/NIK cascade
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“Nrf2 is amember of theCNC-basic leucine zipper (CNC-bZIP) family of transcription factors, which coordinately regulates the constitutive and inducible expression of antioxidant and phase 2 detoxification enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), via a cis-acting DNA element…”
BackgroundNF-κB activation by reactive oxygen species: Fifteen years later
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Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex
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Duration of Nuclear NF-κB Action Regulated by Reversible Acetylation
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Hayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.001 · Cited by 2,654
“…(Paul et al., 2018) and overexpression of the NF-κB p65/RelA subunit antagonizes NRF2 by depriving it of CBP and recruiting histone deacetylase 3 (Liu et al., 2008) and that, when oxidative stress is sufficient to cause DNA damage, the ensuing activation of TP53 results in antagonism of NRF2,…”
BackgroundNrf2 signaling pathway: pivotal roles in inflammation
Ahmed, S. M. U., Luo, L., Namani, A., Wang, X. J., & Tang, X. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.005 · Cited by 1,794
An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation
Saha, S., Buttari, B., Panieri, E., Profumo, E., & Saso, L. (2020) · Molecules · doi:10.3390/molecules25225474 · Cited by 1,460
Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways
Wardyn, J. D., Ponsford, A. H., & Sanderson, C. M. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150014 · Cited by 1,200
Lingappan, K. (2018) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2017.11.002 · Cited by 1,051
“On the other hand, NF-κB inhibits Nrf2 by competing for the transcriptional co-activator CBP (CREB-binding protein)–p300 complex [30].”
Background
Metadata
- Authors
- Liu, G.-H., Qu, J., & Shen, X.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Shen, Xun
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 1783
- Issue
- 5
- Pages
- 713-727
- ISSN
- 0167-4889 (ISSN-L)
- OpenAlex
- W2113024198
- Cited by
- 697
- References
- 77
- Citations by year
- 2026: 54 · 2025: 45 · 2024: 51 · 2023: 47 · 2022: 68 · 2021: 51 · 2020: 59 · 2019: 59 · 2018: 47 · 2017: 38 · 2016: 32 · 2015: 33 · 2014: 15 · 2013: 28 · 2012: 13
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1904 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30330250, 30570462)
- Shanghai Municipal Education Commission (E-04010)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- NF-κB p65, Nrf2, antioxidant response element, CBP, HDAC3, MafK, heme oxygenase-1, transcriptional repression, histone deacetylation, histone hypoacetylation, PKA phosphorylation, corepressor recruitment, anti-inflammatory signaling
- MeSH terms
- Histone Deacetylase 3, Antioxidants, Cell Line, Gene Expression Regulation, Histone Deacetylases, Humans, Transcription, Genetic, Trans-Activators, NF-kappa B, Response Elements, CREB-Binding Protein, MafK Transcription Factor, NF-E2-Related Factor 2, Transcription Factor RelA
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