Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1.

Abstract

Monoamine oxidase (MAO) A is a key enzyme for the degradation of neurotransmitters serotonin, norepinephrine, and dopamine. There are three consensus glucocorticoid/androgen response elements and four Sp1-binding sites in the human monoamine oxidase A 2-kb promoter. A novel transcription factor R1 (RAM2/CDCA7L) interacts with Sp1-binding sites and represses MAO A gene expression. Luciferase assays show that glucocorticoid (dexamethasone) and androgen (R1881) increase MAO A promoter and catalytic activities in human neuroblastoma and glioblastoma cells. Gel-shift analysis demonstrates that glucocorticoid/androgen receptors interact directly with the third glucocorticoid/androgen response element. Glucocorticoid/androgen receptors also interact with Sp1-binding sites indirectly via transcription factor Sp1. In addition, dexamethasone induces R1 translocation from the cytosol to the nucleus in a time-dependent manner in both the neuroblastoma and wild-type UW228 cell lines but not in R1 knock-down UW228 cells. In summary, this study shows that glucocorticoid enhances monoamine oxidase A gene expression by 1) regulation of R1 translocation; 2) direct interaction of the glucocorticoid receptor with the third glucocorticoid/androgen response element; and 3) indirect interaction of glucocorticoid receptor with the Sp1 or R1 transcription factor on Sp1-binding sites of the MAO A promoter. Androgen also up-regulates MAO A gene expression by direct interaction of androgen receptor with the third glucocorticoid/androgen response element. Androgen receptor indirectly interacts with the Sp1, but not R1 transcription factor, on Sp1-binding sites. This study provides new insights on the differential regulation of MAO A by glucocorticoid and androgen.

• Authors: Xiao-Ming Ou, Kevin Chen, Jean C Shih
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 30 Pg. 21512-21525 (Jul 28 2006) ISSN: 0021-9258 [Print] United States
• PMID: 16728402 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• CDCA7L protein, human
• Glucocorticoids
• Receptors, Androgen
• Repressor Proteins
• Sp1 Transcription Factor
• Transcription Factors
• Monoamine Oxidase

Topics

• Androgens (metabolism)
• Base Sequence
• Cell Line, Tumor
• Gene Expression Regulation
• Gene Expression Regulation, Enzymologic
• Glioblastoma (metabolism)
• Glucocorticoids (chemistry)
• Humans
• Molecular Sequence Data
• Monoamine Oxidase (chemistry)
• Neuroblastoma (metabolism)
• Receptors, Androgen (metabolism)
• Repressor Proteins (chemistry, metabolism)
• Sp1 Transcription Factor (chemistry)
• Transcription Factors (chemistry)