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Research ArticleArticle

Regulation of Human Monoamine Oxidase B Gene by Sp1 and Sp3

Wai K. Wong, Kevin Chen and Jean C. Shih
Molecular Pharmacology April 2001, 59 (4) 852-859; DOI: https://doi.org/10.1124/mol.59.4.852
Wai K. Wong
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Kevin Chen
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Jean C. Shih
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Abstract

The human monoamine oxidase (MAO) B plays a major role in the degradation of biogenic and dietary amines such as phenylethylamine, benzylamine, dopamine, and tyramine. We previously showed that the −246/−99 MAO B promoter region exhibited the highest activity and contained two clusters of overlapping Sp1 sites, a CACCC element and a TATA box. Here, using a series of 10 deletion constructs of the 2-kilobase pair 5′-flanking sequence, we identified additional potential regulatory elements, including activator proteins 1 and 4, CAAT, GATA, upstream stimulatory factor (USF), estrogen receptor (ER), and sex-determining region Y-box 5 (SOX5). Analysis of nine site-directed mutations of −246/−99 region reveals that both clusters of Sp1 sites contribute positively whereas the CACCC element contributes negatively to the transcriptional activity. Gel shift analysis demonstrates that in addition to Sp1, Sp3 can interact with both clusters of Sp1 sites. Cotransfection experiments show that Sp1 and its closely related family member Sp4 cantrans-activate MAO B promoter activity through the proximal cluster of Sp1 sites and its activation can be repressed by the over-expression of Sp3 and a related family member BTEB2. These results suggest that the binding to the overlapping Sp1 sites by various members of Sp family is important for the regulation of the MAO B gene expression.

Footnotes

    • Received August 29, 2000.
    • Accepted January 4, 2001.
  • Send reprint requests to: Prof. Jean C. Shih, Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, PSC 528, Los Angeles, California 90033. E-mail: jcshih{at}usc.edu

  • This work was supported by National Institutes of Mental Health Grants R01-MH37020, R37-MH39085 (MERIT Award), K05-MH00796 (Research Scientist Award), and the Welin Professorship.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 59 (4)
Molecular Pharmacology
Vol. 59, Issue 4
1 Apr 2001
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Research ArticleArticle

Regulation of Human Monoamine Oxidase B Gene by Sp1 and Sp3

Wai K. Wong, Kevin Chen and Jean C. Shih
Molecular Pharmacology April 1, 2001, 59 (4) 852-859; DOI: https://doi.org/10.1124/mol.59.4.852

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Research ArticleArticle

Regulation of Human Monoamine Oxidase B Gene by Sp1 and Sp3

Wai K. Wong, Kevin Chen and Jean C. Shih
Molecular Pharmacology April 1, 2001, 59 (4) 852-859; DOI: https://doi.org/10.1124/mol.59.4.852
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