ArticleThe Journal of biological chemistry2010
Nuclear factor kappaB- and specificity protein 1-dependent p53-mediated bi-directional regulation of the human manganese superoxide dismutase gene.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- A Scorpion Venom-Derived Peptide M6 Endowed with Anti-Aging Ability via Enhanced Antioxidant Activity in Cells,International journal of biological sciences · 2026Article
- 4-Furanylvinylquinoline derivative as a new scaffold for the design of oxidative stress initiator and glucose transporter inhibitor drugs.Scientific reports · 2024Article
- Determination of dose- and time-dependent hepatotoxicity and apoptosis of Lanthanum oxide nanoparticles in female Swiss albino mice.Environmental science and pollution research international · 2024Article
- Manganese Superoxide Dismutase Dysfunction and the Pathogenesis of Kidney Disease.Frontiers in physiology · 2020Review
- UVB-induced inactivation of manganese-containing superoxide dismutase promotes mitophagy via ROS-mediated mTORC2 pathway activation.The Journal of biological chemistry · 2019Article
- Induced Trf2 deletion leads to aging vascular phenotype in mice associated with arterial telomere uncapping, senescence signaling, and oxidative stress.Journal of molecular and cellular cardiology · 2019Article
- Insights into the Dichotomous Regulation of SOD2 in Cancer.Antioxidants (Basel, Switzerland) · 2017Review
- N-acetyl-L-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing.Molecular biology reports · 2016Article
- Antihelminthic benzimidazoles are novel HIF activators that prevent oxidative neuronal death via binding to tubulin.Antioxidants & redox signaling · 2015Article
- p53 and mitochondrial function in neurons.Biochimica et biophysica acta · 2014Review
- Loss of p27 upregulates MnSOD in a STAT3-dependent manner, disrupts intracellular redox activity and enhances cell migration.Journal of cell science · 2014Article
- MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx.Antioxidants & redox signaling · 2014Review
- FUsed in sarcoma is a novel regulator of manganese superoxide dismutase gene transcription.Antioxidants & redox signaling · 2014Article
- The transcription factor p53: not a repressor, solely an activator.Cell cycle (Georgetown, Tex.) · 2014Article
- Mitochondrial p53 mediates a transcription-independent regulation of cell respiration and interacts with the mitochondrial F₁F0-ATP synthase.Cell cycle (Georgetown, Tex.) · 2013Article
- Conditional radioresistance of Tet-inducible manganese superoxide dismutase bone marrow stromal cell lines.Radiation research · 2013Article
- Curbing cancer's sweet tooth: is there a role for MnSOD in regulation of the Warburg effect?Mitochondrion · 2013Review
- Lack of p53 decreases basal oxidative stress levels in the brain through upregulation of thioredoxin-1, biliverdin reductase-A, manganese superoxide dismutase, and nuclear factor kappa-B.Antioxidants & redox signaling · 2012Article
- Oxidative Stress Induced by MnSOD-p53 Interaction: Pro- or Anti-Tumorigenic?Journal of signal transduction · 2012Article
- Manganese superoxide dismutase is a p53-regulated gene that switches cancers between early and advanced stages.Cancer research · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Tumor suppressor p53 is known to activate certain sets of genes while suppressing others. However, whether p53 can both activate and suppress the same gene is unclear. To address this question, concentration-dependent p53 effect on the manganese superoxide dismutase (MnSOD) gene was investigated. By transfecting p53 in PC-3 cells, we demonstrate that low concentrations of p53 increase while high concentrations suppress MnSOD expression. The physiological relevance of this effect was determined in vitro and in vivo using combined UVB-mediated activation and small interference RNA-mediated suppression of p53. Results were consistent with the bi-directional effect of p53 on MnSOD expression. MnSOD-promoter/enhancer analysis demonstrates that p53 is suppressive to the promoter activity regardless of the presence or absence of putative p53 binding sites. However, a low level of p53 increases MnSOD gene transcription in the presence of the intronic-enhancer element, and this effect is dependent on nuclear-factor kappaB (NF-kappaB) binding sites. Expression of p53 enhances nuclear levels of p65 with corresponding increase in the DNA-binding activity of NF-kappaB as detected by electrophoretic mobility shift and chromatin immunoprecipitation assays. Transfection of p65 small interference RNA reduces the positive effect of p53 on MnSOD gene transcription. These data suggest that p65 can overcome the negative effect of p53 on MnSOD expression. However, when the level of p53 was further increased, the suppressive effect of p53 outweighed the positive effect of p65 and led to the suppression of MnSOD gene transcription. These results demonstrated that p53 can both suppress and induce MnSOD expression depending on the balance of promoter and enhancer binding transcription factors.
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Registered trials
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