ArticleThe Journal of biological chemistry2006
Specificity protein 1-dependent p53-mediated suppression of human manganese superoxide dismutase gene expression.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 111 citations in OpenAlex.
- Alternative Approaches and Plant-Based Remedies for Livestock Health Management Among the Batswana of Southern Africa: A Review.Chemistry & biodiversity · 2026Review
- Manganese Superoxide Dismutase: Structure, Function, and Implications in Human Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Nucleophosmin 1 promotes mucosal immunity by supporting mitochondrial oxidative phosphorylation and ILC3 activity.Nature immunology · 2024Article
- Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Mitochondrial superoxide targets energy metabolism to modulate epigenetic regulation of NRF2-mediated transcription.Free radical biology & medicine · 2022Article
- p53-Mediated Indirect Regulation on Cellular Metabolism: From the Mechanism of Pathogenesis to the Development of Cancer Therapeutics.Frontiers in oncology · 2022Review
- C-Reactive Protein and High-Sensitive Cardiac Troponins Correlate with Oxidative Stress in Valvular Heart Disease Patients.Oxidative medicine and cellular longevity · 2022Article
- Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish.Cell death & disease · 2021Article
- Possible Beneficial Effects of N-Acetylcysteine for Treatment of Triple-Negative Breast Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- Evaluation of the Response of HOS and Saos-2 Osteosarcoma Cell Lines When Exposed to Different Sizes and Concentrations of Silver Nanoparticles.BioMed research international · 2021Article
- Cordycepin inhibits the proliferation of malignant peripheral nerve sheath tumor cells through the p53/Sp1/tubulin pathway.American journal of cancer research · 2021Article
- p53 isoform Δ113p53 promotes zebrafish heart regeneration by maintaining redox homeostasis.Cell death & disease · 2020Article
- Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer.Molecular metabolism · 2020Review
- Manganese Superoxide Dismutase Dysfunction and the Pathogenesis of Kidney Disease.Frontiers in physiology · 2020Review
- RGNNV-induced cell cycle arrest at G1/S phase enhanced viral replication via p53-dependent pathway in GS cells.Virus research · 2018Article
- Insights into the Dichotomous Regulation of SOD2 in Cancer.Antioxidants (Basel, Switzerland) · 2017Review
- Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression.Oncogenesis · 2017Article
- ΔNp63 targets cytoglobin to inhibit oxidative stress-induced apoptosis in keratinocytes and lung cancer.Oncogene · 2016Article
- Neuroprotective Effect of Radix Trichosanthis Saponins on Subarachnoid Hemorrhage.Evidence-based complementary and alternative medicine : eCAM · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Manganese superoxide dismutase (MnSOD) is a primary antioxidant enzyme necessary for the survival of aerobic life. Previously, we demonstrated that specificity protein 1 (Sp1) is essential for the basal transcription of the MnSOD gene. We also identified nucleophosmin (NPM), an RNA-binding protein, as an important co-activator of NF-kappaB in the induction of MnSOD by cytokine and tumor promoter. Here, using chromatin immunoprecipitation (ChIP) analysis, we demonstrate that Sp1 and NPM interact in vivo to enhance NF-kappaB-mediated MnSOD induction. Interaction between NPM and Sp1 or NF-kappaB at the promoter and enhancer of the MnSOD gene in vivo were verified by the presence of the PCR products from the promoter and enhancer elements in the ChIP assay. Unexpectedly, we also found p53, another transcription factor, to be a component of the complex detected by ChIP assay. The presence of p53 in this transcription complex was verified by immunoprecipitation of p53 proteins with antibody to Sp1 in nuclear extracts. Using a vector expressing full-length p53 cDNA, we demonstrated that p53 overexpression suppresses MnSOD mRNA and protein levels. Consistent with the negative role of p53 in the expression of the MnSOD gene, expression of small interfering RNA for p53 leads to an increase of MnSOD mRNA and protein levels. Using ChIP assays and immunoprecipitation, we further demonstrated that p53 interacts with Sp1 to suppress both the constitutive and 12-O-tetradecanoylphorbol-13-acetate-stimulated expression of the MnSOD gene. Inhibition of the MnSOD gene by p53 was abolished when Sp1 sites on the MnSOD promoter were mutated or when the Sp1 protein was reduced by siRNA approaches. Because expression of MnSOD protects against cell death, our findings reveal a previously unrecognized mechanism of p53-mediated cell death and demonstrate an intricate relationship between the positive and negative control of MnSOD expression.
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