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dc.contributor.authorYong XUen_US
dc.contributor.authorSureerut Porntadavityen_US
dc.contributor.authorDaret K St Clairen_US
dc.date.accessioned2015-02-02T03:42:24Z-
dc.date.accessioned2017-06-20T16:08:14Z-
dc.date.available2015-02-02T03:42:24Z-
dc.date.available2017-06-20T16:08:14Z-
dc.date.issued2002-
dc.identifier.citationBiochemical Journal. Vol.362, 2002, 401-412en_US
dc.identifier.urihttp://repository.li.mahidol.ac.th/dspace/handle/123456789/2080-
dc.description.abstractManganese superoxide dismutase (MnSOD) plays an important role in regulating cellular redox conditions. Expression of MnSOD has been shown to protect against damage by oxidative stress and to suppress the malignant phenotype of human cancer cells. We have previously cloned the human MnSOD (SOD2) gene and analysed its 5' proximal promoter, which has been characterized by a lack of a TATA or CAAT box and the presence of multiple GC boxes. To define further the molecular mechanisms for the regulation of MnSOD expression, multiple transcription factor-binding motifs containing overlapping specificity protein 1 (Sp1)- and activator protein (AP)-2-binding sites were identified by DNase I footprinting analysis. Functional studies in three cell lines with different levels of Sp1 and AP-2 proteins suggested that the cellular levels of these proteins may differentially regulate transcription via GC-binding motifs in the human SOD2 promoter. Co-transfection of an Sp1 expression vector resulted in an increase in the transcription of the promoter-driven reporter gene. In contrast, co-transfection of the AP-2 expression vector caused a decrease in transcription. Direct mutagenesis analysis of Sp1- and AP-2-binding sites showed that Sp1 is essential for transcription of the human SOD2 gene, whereas AP-2 plays a negative role in the transcription. Immunoprecipitation of Sp1 and AP-2 proteins demonstrated that Sp1 interacts with AP-2 in vivo. Two-hybrid analysis revealed that interaction between Sp1 and AP-2 plays both a positive and negative role in the transcription of the reporter gene in vivo. Taken together, our data indicate that AP-2 down-regulates transcription of the human SOD2 gene via its interaction with Sp1 within the promoter region. These findings, coupled with our previous observation that several cancer cell lines have mutations in the promoter region of the human MnSOD gene, which lead to an increase in an AP-2-binding site and a decrease in the promoter activity, signal the importance of understanding the promoter structure and the regulation of the human SOD2 gene by Sp1 and AP-2.en_US
dc.language.isoenen_US
dc.subjectenzyme inductionen_US
dc.subjectoxidative stressen_US
dc.subjecttumour suppressor geneen_US
dc.subjectOpen Access articleen_US
dc.titleTranscriptional regulation of the human manganese superoxide dismutase gene: the role of specificity protein 1 (Sp1) and activating protein-2 (AP-2)en_US
dc.typeArticleen_US
dc.rights.holderBiochem J.en_US
dc.identifier.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222401/-
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