Cited by 167Genomics, phytochemicals, and oxidative stressNF-κB Signaling PathwaysSignaling Pathways in Disease

Regulatory Potential for Concerted Modulation of Nrf2- and Nfkb1-Mediated Gene Expression in Inflammation and Carcinogenesis

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Nair, S, Doh, S T, Chan, J Y, Kong, A-N, Cai, L·2008·British Journal of Cancer

Abstract

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).”

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  1. Barve A, Khor TO, Nair S, Lin W, Yu S, Jain MR, Chan JY, Kong AN (2008) Pharmacogenomic profile of soy isoflavone concentrate in the prostate of Nrf2 deficient and wild-type mice. J Pharm Sci 97(10): 4528–4545 18236473

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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
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
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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