Regulatory Potential for Concerted Modulation of Nrf2- and Nfkb1-Mediated Gene Expression in Inflammation and Carcinogenesis
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Many studies have implicated nuclear factor E2-related factor 2 (Nrf2) and nuclear factor-kappaB1 (Nfkb1) in inflammation and cancer. However, the regulatory potential for crosstalk between these two important transcription factors in inflammation and carcinogenesis has not been explored. To delineate conserved transcription factor-binding site signatures, we performed bioinformatic analyses on the promoter regions of human and murine Nrf2 and Nfkb1. We performed multiple sequence alignment of Nrf2 and Nfkb1 genes in five mammalian species - human, chimpanzee, dog, mouse and rat - to explore conserved biological features. We constructed a canonical regulatory network for concerted modulation of Nrf2 and Nfkb1 involving several members of the mitogen-activated protein kinase (MAPK) family and present a putative model for concerted modulation of Nrf2 and Nfkb1 in inflammation/carcinogenesis. Our results reflect potential for putative crosstalk between Nrf2 and Nfkb1 modulated through the MAPK cascade that may influence inflammation-associated etiopathogenesis of cancer. Taken together, the elucidation of potential relationships between Nrf2 and Nfkb1 may help to better understand transcriptional regulation, as well as transcription factor networks, associated with the etiopathogenesis of inflammation and cancer.
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Decreased levels of Nrf2, a transcription factor negatively regulated by NF-κB and involved in antioxidant response mechanisms, have been reported in brains of Alzheimer's disease patients.
“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 Nair et al., 2008
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- Authors
- Nair, S., Doh, S. T., Chan, J. Y., Kong, A.-N., & Cai, L.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- University of California, Irvine (US)
- Corresponding author
- Cai, L
- Venue
- British Journal of Cancer
- Published
- 2008-12
- Volume
- 99
- Issue
- 12
- Pages
- 2070-2082
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2607222
- OpenAlex
- W2059649811
- Cited by
- 167
- References
- 58
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 8 · 2020: 13 · 2019: 13 · 2018: 10 · 2017: 16 · 2016: 13 · 2015: 11 · 2014: 7 · 2013: 8 · 2012: 10
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Cancer Institute (CA133675, R01CA094828, R21CA133675)
- National Institute of Environmental Health Sciences (P30ES005022)
- 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 › Signaling Pathways in Disease
- Keywords
- Nrf2, NFKB1, transcription factor crosstalk, inflammation, carcinogenesis, MAPK signaling, transcription factor binding sites, promoter analysis, transcriptional regulation, inflammation-associated cancer
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Cell Transformation, Neoplastic, Humans, Inflammation, Molecular Sequence Data, Gene Expression Regulation, Neoplastic, Sequence Alignment, Conserved Sequence, Computational Biology, Microarray Analysis, NF-E2-Related Factor 2, Mice, Rats, NF-kappa B p50 Subunit
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