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Retinoic acid activates monoamine oxidase B promoter in human neuronal cells.

Abstract
Monoamine oxidase (MAO) B deaminates a number of biogenic and dietary amines and plays an important role in many biological processes. Among hormonal regulations of MAO B, we have recently found that retinoic acid (RA) significantly activates both MAO B promoter activity and mRNA expression in a human neuroblastoma BE(2)C cell line. RA activates MAO B promoter in both concentration- and time-dependent manners, which is mediated through retinoic acid receptor alpha (RARalpha) and retinoid X receptor alpha (RXRalpha). There are four retinoic acid response elements (RAREs) as identified in the MAO B 2-kb promoter, and mutation of the third RARE reduced RA-induced MAO B promoter activation by 50%, suggesting this element is important. Electrophoretic mobility shift analysis and chromatin immunoprecipitation assay demonstrated that RARalpha specifically binds to the third RARE both in vitro and in vivo. Moreover, transient transfection and luciferase assays revealed that Sp1 enhances but not essentially required for the RA activation of MAO B through two clusters of Sp1-binding sites in the MAO B promoter. RARalpha physically interacts with Sp1 via zinc finger domains in Sp1 as determined by co-immunoprecipitation assay. Further, RARalpha was shown to be recruited by Sp1 and to form a transcriptional regulation complex with Sp1 in the Sp1-binding sites of natural MAO B promoter. Taken together, this study provides evidence for the first time showing the stimulating effect of RA on MAO B and new insight into the molecular mechanisms of MAO B regulation by hormones.
AuthorsJason B Wu, Kevin Chen, Xiao-Ming Ou, Jean C Shih
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 25 Pg. 16723-16735 (Jun 19 2009) ISSN: 1083-351X [Electronic] United States
PMID19401466 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA Primers
  • RARA protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Retinoic Acid
  • Recombinant Fusion Proteins
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptor alpha
  • Sp1 Transcription Factor
  • Tretinoin
  • Monoamine Oxidase
Topics
  • Base Sequence
  • Binding Sites (genetics)
  • Cell Line
  • DNA Primers (genetics)
  • Humans
  • Monoamine Oxidase (genetics)
  • Mutagenesis, Site-Directed
  • Neurons (drug effects, enzymology)
  • Promoter Regions, Genetic (drug effects)
  • RNA Interference
  • RNA, Messenger (genetics, metabolism)
  • RNA, Small Interfering (genetics)
  • Receptors, Retinoic Acid (metabolism)
  • Recombinant Fusion Proteins (metabolism)
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptor alpha (metabolism)
  • Sp1 Transcription Factor (metabolism)
  • Tretinoin (pharmacology)

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