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Titolo:
Regulation of human monoamine oxidase B gene by Sp1 and Sp3
Autore:
Wong, WK; Chen, K; Shih, JC;
Indirizzi:
Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90033 USA Univ So Calif Los Angeles CA USA 90033 Toxicol, Los Angeles, CA 90033 USA Univ So Calif, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA Univ So Calif Los Angeles CA USA 90033 urobiol, Los Angeles, CA 90033 USA
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 4, volume: 59, anno: 2001,
pagine: 852 - 859
SICI:
0026-895X(200104)59:4<852:ROHMOB>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSCRIPTIONAL REGULATION; PROMOTER; BRAIN; MAO; ORGANIZATION; ACTIVATION; DISEASE; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Shih, JC Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, 1985 Zonal Ave,PSC528, Los Angeles, CA 90033 USA Univ So Calif 1985 Zonal Ave,PSC 528 Los Angeles CA USA 90033 USA
Citazione:
W.K. Wong et al., "Regulation of human monoamine oxidase B gene by Sp1 and Sp3", MOLEC PHARM, 59(4), 2001, pp. 852-859

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 can trans-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.

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Documento generato il 02/04/20 alle ore 06:04:27