ArticleMolecular cancer research : MCR2008
Mutations in the SOD2 promoter reveal a molecular basis for an activating protein 2-dependent dysregulation of manganese superoxide dismutase expression in cancer cells.
Article in Molecular cancer research : MCR, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Manganese Superoxide Dismutase: Structure, Function, and Implications in Human Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Gα13 Promotes Clonogenic Growth by Increasing Tolerance to Oxidative Metabolic Stress in Prostate Cancer Cells.International journal of molecular sciences · 2025Article
- GPCR-Gα13 Involvement in Mitochondrial Function, Oxidative Stress, and Prostate Cancer.International journal of molecular sciences · 2024Review
- Human papillomavirus and cervical cancer: an insight highlighting pathogenesis and targeting strategies.Virusdisease · 2022Review
- Oxidative stress: therapeutic approaches for cervical cancer treatment.Clinics (Sao Paulo, Brazil) · 2018Review
- Insights into the Dichotomous Regulation of SOD2 in Cancer.Antioxidants (Basel, Switzerland) · 2017Review
- Domain Mapping of Heat Shock Protein 70 Reveals That Glutamic Acid 446 and Arginine 447 Are Critical for Regulating Superoxide Dismutase 2 Function.The Journal of biological chemistry · 2017Article
- Mitochondrial common deletion is elevated in blood of breast cancer patients mediated by oxidative stress.Mitochondrion · 2016Article
- Mitochondrial Dysfunction Due to Lack of Manganese Superoxide Dismutase Promotes Hepatocarcinogenesis.Antioxidants & redox signaling · 2015Article
- Signatures of accelerated somatic evolution in gene promoters in multiple cancer types.Nucleic acids research · 2015Article
- Host genetic variations in glutathione-S-transferases, superoxide dismutases and catalase genes influence susceptibility to malaria infection in an Indian population.Molecular genetics and genomics : MGG · 2015Article
- Identification of novel pathogenic copy number aberrations in multiple myeloma: the Malaysian context.Molecular cytogenetics · 2014Article
- NFκB1 (p50) suppresses SOD2 expression by inhibiting FoxO3a transactivation in a miR190/PHLPP1/Akt-dependent axis.Molecular biology of the cell · 2013Article
- Superior therapeutic index of calmangafodipir in comparison to mangafodipir as a chemotherapy adjunct.Translational oncology · 2012Article
- A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease.Brain and behavior · 2012Article
- Manganese superoxide dismutase: beyond life and death.Amino acids · 2012Review
- Dual function of protein kinase C (PKC) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced manganese superoxide dismutase (MnSOD) expression: activation of CREB and FOXO3a by PKC-alpha phosphorylation and by PKC-mediated inactivation of Akt, respectively.The Journal of biological chemistry · 2011Article
- Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior.Journal of Zhejiang University. Science. B · 2011Article
- Manganese superoxide dismutase: effect of the ala16val polymorphism on protein, activity, and mRNA levels in human breast cancer cell lines and stably transfected mouse embryonic fibroblasts.Molecular and cellular biochemistry · 2010Article
- Regulation of superoxide dismutase genes: implications in disease.Free radical biology & medicine · 2009Review
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
A primary antioxidant enzyme in mitochondria, manganese superoxide dismutase (MnSOD), plays a critical role in the survival of aerobic life. It is well documented that, compared with normal cell counterparts, MnSOD level is decreased in neoplastic transformed cells but is increased in aggressive cancers. However, the underlying mechanism for the observed dysregulation of MnSOD in cancer is unknown. We have identified previously a unique set of mutations located in the promoter region of the SOD2 gene in several types of cancer cells. We found that a C-to-T transition at -102 and an insertion of A at -93 down-regulate MnSOD transcription by interrupting the formation of a single-stranded loop that is essential for a high level of promoter activity. Here, we show that the additional downstream mutation, C-to-G transversion at -38, creates a binding site for the transcription factors specificity protein 1 (Sp1) and activating protein 2 (AP-2). The promoter function is regulated by the relative levels of Sp1 and AP-2. In cytokine-induced expression of the SOD2 gene, Sp1 cooperates with a transcriptional complex containing nuclear factor-kappaB and nucleophosmin. The presence of AP-2 attenuates this induction. Our results suggest that the high level of MnSOD observed in aggressive cancer cells may be due, in part, to the absence of AP-2 transcriptional repression.
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