Cited by 699Genomics, phytochemicals, and oxidative stressNF-κB Signaling PathwaysNuclear Receptors and Signaling

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

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Liu, Guang-Hui, Qu, Jing, Shen, Xun·2008·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

DOI 10.1016/j.bbamcr.2008.01.002

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Abstract

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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Cytokines suppress adipogenesis and PPAR-γ function through the TAK1/TAB1/NIK cascade
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Retracted
Signaling to NF-κB
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Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
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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…”
Background
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Background
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Background
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Background
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Background
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BackgroundResult
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Method
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“…B p65 is likely mediated by its methylation at lysine 310 (Levy et al., 2011), miRNAs (Lee et al., 2014; Lukiw, 2022) and interactions with other transcriptional factors such as FOXO (Belguise and Sonenshein, 2007; Liu et al., 2008; Hwang et al., 2010) etc., which still need further investigation.”
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Towards an Integrated View of Early Molecular Changes Underlying Vulnerability to Social Stress in Psychosis
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“For example, microglia generate ROS to destroy pathogens, which is also toxic for neurons and can sensitize the brain to more damage by activating signaling molecules such as NF-κB, consistent with the neuroprogression of psychosis [68].”
BackgroundInfluential
The flavonoids extract from Okra flowers protects against DSS-induced colitis via regulating NF-κB signaling pathway and gut microbiota
Huang, X., Li, X., Deng, Y., Zhou, T., Chen, T., Wu, S., Xia, R., Kang, Y., & Yin, W. (2022) · Journal of Functional Foods · doi:10.1016/j.jff.2022.105335 · Cited by 6
Neurodegeneration from Drugs and Aging‐Derived Free Radicals
Ramkissoon, A., Shapiro, A. M., Loniewska, M. M., & Wells, P. G. (2013) · Wiley eBooks · doi:10.1002/9781118355886.ch10 · Cited by 6
Processed Scutellaria baicalensis Georgi Extract Alleviates LPS-Induced Inflammatory and Oxidative Stress through a Crosstalk between NF-κB and KEAP1/NRF2 Signaling in Macrophage Cells
Ali, A., Kim, E. H., Lee, J.-H., Leem, K., Seong, S., & Kim, W. (2021) · Applied Sciences · doi:10.3390/app11136055 · Cited by 5
Interplay of Cellular Nrf2/NF-κB Signalling after Plasma Stimulation of Malignant vs. Non-Malignant Dermal Cells
Manzhula, K., Rebl, A., Budde, K., & Rebl, H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252010967 · Cited by 6
“Specifically, p65 can inhibit Nrf2 by competitively interacting with the transcriptional co-activator CREB binding protein (CBP) and by promoting the recruitment of histone deacetylase 3, a co-repressor, to ARE [111].”
Background
Coenzyme Q10 protects against glyphosate-based herbicide-induced testicular and sperm toxicity by modulating Nrf2/Keap1/HO-1 and TLR4/NF-κB pathways
Mutluay, D., Özbek, K. Ç., Yücel, G., Güngör, Ş., Yakut, S., Denk, B., & Kara, A. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04724-5 · Cited by 5
Kynurenine Pathway, Nrf2 and NF-κB Cross-Regulation in the CNS: An Overview
Cerdán-Centeno, K. T., González-Soto, A. Y., Lares-López, V., Sánchez-Vázquez, L. D., Tapia-Estrada, H. R., Túnez, I., López-Goerne, T. M., Tinkov, A. A., Aschner, M., & Santamarı́a, A. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05802-2 · Cited by 5
The role of NF-κB in diabetic cardiomyopathy
Liu, H.-J., Gui, L.-K., Wei, H., Zhou, X., Liu, Z.-L., & Jin, L. F. (2024) · All Life · doi:10.1080/26895293.2024.2397402 · Cited by 5
Orange peel ethanolic extract and physical exercise prevent testicular toxicity in streptozocin and high fat diet-induced type 2 diabetes rats via Nrf2/NF-kB signaling: In silico and in vivo studies
Odetayo, A. F., Ajibare, A. J., Okesina, K. B., Akhigbe, T. M., Olugbogi, E. A., & Olayaki, L. A. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e39780 · Cited by 5
“Furthermore, overexpression of NF-κ B can suppress the transcriptional activity of Nrf2, thereby leading to oxidative stress [71].”
TACIMA-218: A Novel Pro-Oxidant Agent Exhibiting Selective Antitumoral Activity
Abusarah, J., Cui, Y., El-Hachem, N., El-Kadiry, A. E.-H., Hammond-Martel, I., Würtele, H., Beaudry, A., Raynal, N. J. ‐., Robert, F., Pelletier, J., et al. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0333 · Cited by 5
“This is a plausible hypothesis given that class 1 histone deacetylases were reported to inhibit Nrf2 binding to ARE by maintaining a state of histone hypoacetylation (49, 50).”
Background
IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Evidence for reproductive health effects following exposure to hydraulic fracturing chemical mixtures
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Redox State in Professional Cyclists Following Competitive Sports Activity
Corsetti, R. (2012) · The Open Sports Medicine Journal · doi:10.2174/1874387001206010034 · Cited by 5
“Conclusions: Redox balance assessment is a useful tool to: a) monitor athletic performance and predict the onset of redox inflammatory state (RI), which might be detrimental to the athlete's physical condition; b) propose suitable supplementation with particular foods and dietary supplements.”
Method
Nrf2 Pathway Involvement in the Beneficial Skin Effects of Moderate Ionic Osmotic Stress – the Case of the Dead Sea Water
Cohen, D., Ma’or, Z., Cohen, M. P., Oron, M., & Kohen, R. (2022) · Journal of Cosmetics Dermatological Sciences and Applications · doi:10.2139/ssrn.4025899 · Cited by 5
Liver Diseases: Epigenetic Mechanisms, Oxidative Stress and Use of Alpha-Lipoic Acid
Uskoković, A. S., Dinić, S., Јovanović, J. A., Poznanović, G., Vidaković, M., & Mihailović, M. (2017) · Springer eBooks · doi:10.1007/978-3-319-31143-2_112-1 · Cited by 5
“Nuclear factor erythroid 2-related factor 2 (Nrf2), a major transcriptional regulator of cellular redox balance, is also an important component of the antioxidant defense system (Tang et al. 2014).”
BackgroundInfluential
Tissue Integrity and COVID-19
Kerch, G. (2021) · Encyclopedia · doi:10.3390/encyclopedia1010020 · Cited by 5
“Activation of Nrf2 can also suppress NF-κB-mediated inflammatory processes in COVID-19 [92], Figure 4.”
BackgroundInfluential
Decoding senescent drivers in Alzheimer's disease: From bench to bedside
Zhou, R., Lin, X., Liao, Z., Lin, J., Zheng, R., Ni, H., Liu, W., Feng, Z., He, Q., Lin, X., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102978 · Cited by 4
Social isolation: an integrated molecular web that disrupts cellular homeostasis
Qaisiya, M., Moretto, E., Battocchio, E., Pistella, A., Caso, M. G., Bellani, M., & Guarnieri, F. C. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1693696 · Cited by 10
Therapeutic potential of isothiocyanates by targeting the NRF2 pathway
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Homoyessotoxin alleviates inflammatory responses by regulating the TLR4/MyD88/NFκB and Nrf2/HO-1 pathways
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Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain by Activation of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 in the Dorsal Root Ganglia
Kim, H. K., Wang, Q., Hwang, S., Dougherty, P. M., Wang, J., & Abdi, S. (2023) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000006736 · Cited by 4
Mechanism of Nrf2 in the treatment of ulcerative colitis via regulating macrophage polarization.
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Okanin alleviates symptoms of nociceptive-like responses in diabetic peripheral neuropathy in type 1 diabetic Wistar rats by regulating the AGEs/NF-κB/Nrf-2 pathway
Ganie, M. R., Khan, N., Shukla, M., Sood, S., Devi, S., Arora, P., Kumar, M., Najar, I. A., & Tang, J. (2024) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2024.11.003 · Cited by 6
Selenium Yeast Alleviates Escherichia coli-Induced Endometritis in Goats Under High Cortisol Background
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Individual and combined use of ginsenoside F2 and cyanidin-3-O-glucoside attenuates H 2 O 2 -induced apoptosis in HEK-293 cells via the NF-κB pathway
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Exercise training improves obesity-induced inflammatory signaling in rat brown adipose tissue
Tsuzuki, T., Yoshihara, T., Ichinoseki‐Sekine, N., Kobayashi, H., Negishi, T., Yukawa, K., & Naıto, H. (2022) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2022.101398 · Cited by 4
“NF-κB can directly inhibit Nrf2-antioxidant response element signaling [27], whereas Nrf2 negatively regulates the NF-κB signaling pathway by increasing antioxidant defense [28].”
Background
Angiotensin II reduces glyoxalase 1 activity and expression in vascular smooth muscle cells: Implications for diabetic vascular complications
Kırça, M., & Yeşilkaya, A. (2023) · Cell Biochemistry and Function · doi:10.1002/cbf.3879 · Cited by 4
“26 Moreover, Ang II ‐ induced Nrf2 activation may occur through STAT3 27 or sestrin2 28 – 30 activation.”
Background
GC-Rich DNA Fragments and Oxidized Cell-Free DNA Have Different Effects on NF-kB and NRF2 Signaling in MSC
Sergeeva, V. A., Kostyuk, S. V., Ershova, E. S., Malinovskaya, E. M., Smirnova, T. D., Kameneva, L. V., & Veiko, N. N. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-42044-8_21 · Cited by 4
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de Klerk, D. J., de Keijzer, M. J., Franchi, L. P., Tian, J., Gureev, M., Ge, Y., Mesquita, B. S., Saelman, G., herteryck, I. V., Dias, L. M., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117620 · Cited by 3
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“Overall, these multiple upstream signaling pathways tightly control Nrf2 activity, ensuring a balanced cellular response to oxidative stress and maintaining redox homeostasis (Liu et al. 2008; Chowdhry et al. 2013; Koundouros and Poulogiannis 2018; Xu et al. 2020; Yu and Xiao 2021).”
Influential
Enhanced Neurophysiological Benefits of Magnesium-Acetyl-Taurate Over Magnesium-L-Threonate: A Comparative pre-clinical Study on Bioavailability, Synaptic Plasticity and Cognitive Functions
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Hydrophobic Components in Light-Yellow Pulp Sweet Potato (Ipomoea batatas (L.) Lam.) Tubers Suppress LPS-Induced Inflammatory Responses in RAW264.7 Cells via Activation of the Nrf2 Pathway
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ZBP-89 reduces histone deacetylase 3 by degrading IkappaB in the presence of Pin1
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“NF-κB subunit p65 has been shown to recruit HDAC3 to the antioxidant response element of Nrf2 gene, leading to local histone hypoacetylation [30].”
Mechanically demanding eccentric exercise increases nuclear factor erythroid 2-related factor 2 activity in human peripheral blood mononuclear cells
Thorley, J., Thomas, C., Bailey, S. J., Martin, N. R. W., BISHOP, N. C., & Clifford, T. (2023) · Journal of Sports Sciences · doi:10.1080/02640414.2023.2263713 · Cited by 4
“In addition, there is concern that muscle biopsies may trigger an acute inflammatory response (i.e., nuclear factor-κB activation) that could independently activate NRF2, thereby affecting the interpretation of transcriptional changes (Groeger et al., 2010; Liu et al., 2008).”
Background
Dendrobium huoshanense stem polysaccharide exhibits gastroprotective effect via regulating PI3K/AKT, NF-κB and Nrf-2 signaling in high-salt diet-induced gastritis mice
Ye, H.-Y., Shang, Z.-Z., Gao, X., Zha, X., Zhang, F., Li, Q.-M., Liu, J., & Luo, J. (2024) · Food Bioscience · doi:10.1016/j.fbio.2024.105309 · Cited by 3
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Contribution of Transcription Factors and Genes in the Induction of Oxidative Stress
Farooqui, A. A. (2014) · Springer eBooks · doi:10.1007/978-3-319-04111-7_9 · Cited by 3
Alterations of the Antioxidant and Inflammatory Response of the Peripheral Blood Granulocytes to SARS-CoV-2 Infection in the Deceased COVID-19 PatientsPreprint
Žarković, N., Biernacki, M., Wójcik, P., Jarocka-Karpowicz, I., Orehovec, B., Baršić, B., Tarle, M., Kmet, M., Lukšić, I., & Skrzydlewska, E. (2022) · Preprints.org · doi:10.20944/preprints202209.0298.v1 · Cited by 3
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A new synbiotic supplementation ameliorates ulcerative colitis via modulating microbial homeostasis, protecting intestinal barrier integrity, and maintaining immunity homeostasis in mice
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Ameliorative impact of sacubitril/valsartan on paraquat-induced acute lung injury: role of Nrf2 and TLR4/NF-κB signaling pathway
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“Conversely, NF-κB p65 has the ability to prevent the activation of Nrf2 by reducing CREB binding protein (CBP), the transcriptional co-activator of Nrf2, and preventing CBP from binding to Nrf2 (Liu et al. 2008).”
JAK2/STAT3 Signaling Pathway Modulates Acute Methylmercury Toxicity in the Mouse Astrocyte C8-D1A Cell Line
Ahmed, A., Wong, M., Santamarı́a, A., da Rocha, J. B. T., Bowman, A. B., Aschner, M., & Ferrer, B. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04507-7 · Cited by 2

Authors: Liu, G.-H., Qu, J., & Shen, X.
Affiliations: Chinese Academy of Sciences (CN)
Corresponding author: Shen, Xun
ORCID: Liu, Guang-Hui
Qu, Jing
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)
DOI: 10.1016/j.bbamcr.2008.01.002
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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NF-κB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK

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