Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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Regulation of MAO-A and MAO-B Gene Expression

Author(s): J. C. Shih and K. Chen

Affiliation: Department of Cell andNeurobiology, Keck School of Medicine, University of SouthernCalifornia, 1985 Zonal Ave. Los Angeles, California, 90033, USA

Keywords: mao a, mao b, gene regulation, promoter, sp1, protein kinase c, mapkinase, egr-1

Abstract:

MAO A and B genes are made of 15 exons with identical exon-intron organization. They are located on X-chromosome organized in opposite direction, tail to tail with 24kb apart. Both promoters are GC-rich and regulated by transcription factor Sp1. However, they have distinctly different features. MAO B gene, but not MAO A gene, has TATA box. MAO B promoter contains two clusters of overlapping Sp1 sites, the CACCC repressor element. Transcription factors Sp1 and Sp4 can 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. Decreased methylation and transcription repressor Sp3 upregulate human MAO B, but not MAO A, gene expression during Caco-2 differentiation. MAO B, but not MAO A gene, could be activated by PMA (phorbol 12-myristate 13-acetate) by protein kinase C, MAPkinase signal transduction pathway involves cJun and Egr-1. The differences in MAO A and B gene regulation may explain the different tissue-specific expression and functions of these two important isoenzymes.

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Article Details

VOLUME: 11
ISSUE: 15
Page: [1995 - 2005]
Pages: 11
DOI: 10.2174/0929867043364757