rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2005-3-21
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pubmed:abstractText |
Monoamine oxidase catalyzes the oxidative deamination of a number of neurotransmitters. A deficiency in monoamine oxidase A results in aggressive behavior in both humans and mice. Studies on the regulation of monoamine oxidase A gene expression have shown that the Sp1 family is important for monoamine oxidase A expression. To search for novel transcription factors, the sequences of three Sp1 sites in the monoamine oxidase A core promoter were used in the yeast one-hybrid system to screen a human cDNA library. A novel repressor, R1 (RAM2), has been cloned. The R1 cDNA encodes a protein with 454 amino acids and an open reading frame at the 5'-end. The transfection of R1 in a human neuroblastoma cell line, SK-N-BE (2)-C, inhibited the monoamine oxidase A promoter and enzymatic activity. The degree of inhibition of monoamine oxidase A by R1 correlated with the level of R1 protein expression. R1 was also found to repress monoamine oxidase A promoter activity within a natural chromatin environment. A gel-shift assay indicated that the endogenous R1 protein in SK-N-BE (2)-C cells interacted with the R1 binding sequence. R1 also bound directly to the natural monoamine oxidase A promoter in vivo as shown by chromatin immunoprecipitation assay. Immunocytochemical analysis showed that R1 was expressed in both cytosol and nucleus, which suggested a role for R1 in transcriptional regulation. Northern blot analysis revealed the presence of endogenous R1 mRNA in human brain and peripheral tissues. Taken together, this study shows that R1 is a novel repressor that inhibits monoamine oxidase A gene expression.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15654081-10202537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15654081-10591056,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/15654081-9326944
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11552-9
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pubmed:dateRevised |
2010-9-24
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pubmed:meshHeading |
pubmed-meshheading:15654081-Amino Acid Sequence,
pubmed-meshheading:15654081-Base Sequence,
pubmed-meshheading:15654081-Blotting, Northern,
pubmed-meshheading:15654081-Catalysis,
pubmed-meshheading:15654081-Cell Line, Tumor,
pubmed-meshheading:15654081-Chromatin,
pubmed-meshheading:15654081-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:15654081-Humans,
pubmed-meshheading:15654081-Immunohistochemistry,
pubmed-meshheading:15654081-Molecular Sequence Data,
pubmed-meshheading:15654081-Monoamine Oxidase,
pubmed-meshheading:15654081-Promoter Regions, Genetic,
pubmed-meshheading:15654081-Repressor Proteins
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pubmed:year |
2005
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pubmed:articleTitle |
R1, a novel repressor of the human monoamine oxidase A.
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pubmed:affiliation |
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of California, Los Angeles, California 90033, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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