Reciprocal down-regulation of p53 and SOD2 gene expression-implication in p53 mediated apoptosis
Abstract
p53 regulates the transcription of a number of genes among which are different redox-related genes. It has been proposed that these genes can induce a cellular oxidative stress leading to p53-dependent apoptosis (Polyak et al., 1997). MnSOD, the product of superoxide dismutase 2 (SOD2) gene, is one of the major cellular defences against oxidative stress. We demonstrate here that p53 is able to repress SOD2 gene expression and that this repression takes place at promoter level. We show the importance of this regulation for the p53 function, by demonstrating that an overexpression of MnSOD decreases p53-mediated induction of apoptosis. Moreover, we demonstrate that MnSOD overexpression decreases p53-gene expression at the promoter level. These findings raise the hypothesis that p53 and SOD2 genes are mutually regulated leading to the modulation of various cellular processes including apoptosis.
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The increase in MnSOD in p53 knockout mice is consistent with p53 transcriptional repression of MnSOD.
“which is consistent with the p53 transcriptional repression of MnSOD [90,91]”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [90]
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References 57 · Cited by 180
- Authors
- Drane, P., Bravard, A., Bouvard, V., & May, E.
- Affiliations
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Bravard, Anne
- Venue
- Oncogene
- Published
- 2001-01-25
- Volume
- 20
- Issue
- 4
- Pages
- 430-439
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2316273706
- Cited by
- 180
- References
- 57
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 12 · 2021: 8 · 2020: 10 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 5 · 2015: 8 · 2014: 8 · 2013: 8 · 2012: 3
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53, manganese superoxide dismutase, gene expression inhibition, promoter regulation, oxidative stress, p53-dependent apoptosis, transcriptional regulation
- MeSH terms
- Breast Neoplasms, Female, Humans, Promoter Regions, Genetic, Superoxide Dismutase, Tumor Cells, Cultured, Down-Regulation, Tumor Suppressor Protein p53, NF-kappa B, Apoptosis, Oxidative Stress
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