Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-4-3
pubmed:abstractText
The synaptosomal-associated protein of 25 kDa (SNAP-25) is a pre-synaptic plasma membrane protein. SNAP-25 plays an important role in synaptic vesicle membrane docking and fusion, which is involved in the regulation of neurotransmitter release. SNAP-25 has been implicated in the pathogenesis of neuropsychiatric disorders including Schizophrenia, attention-deficit hyperactivity disorder and Alzheimer's disease. We cloned a 1584 bp segment of the 5' flanking region of the human SNAP-25 gene. A series of nested deletions of the 5' flanking region fragment were subcloned into the pGL3-basic luciferase reporter plasmid. N2A cells were transfected with the SNAP-25 promoter constructs and luciferase activity was measured as an indication of promoter activity. We identified a 188 bp fragment containing the transcription initiation site as the minimal region necessary for promoter activity. Several putative cis-acting elements including SP1, hypoxia inducible factor (HIF), cAMP-response element binding protein, T-cell factor/lymphocyte enhancer factor 1 (TCF/LEF1), AP1 and the signal transducer and activator of transcription-6 (STAT6) are found in the 5' flanking region of SNAP-25 gene. Transcriptional activation and gel shift assays showed that the human SNAP-25 gene promoter contains functional SP1 response elements. Over-expression of SP1 increased SNAP-25 gene expression and inhibition of SP1-mediated transcriptional activation reduced SNAP-25 gene expression. These results suggest that SP1 plays an important role in regulation of the human SNAP-25 gene expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
512-23
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18194215-Base Sequence, pubmed-meshheading:18194215-Binding Sites, pubmed-meshheading:18194215-Cell Line, Transformed, pubmed-meshheading:18194215-Electrophoretic Mobility Shift Assay, pubmed-meshheading:18194215-Gene Expression, pubmed-meshheading:18194215-Gene Expression Regulation, pubmed-meshheading:18194215-Humans, pubmed-meshheading:18194215-Plicamycin, pubmed-meshheading:18194215-Promoter Regions, Genetic, pubmed-meshheading:18194215-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:18194215-Sequence Deletion, pubmed-meshheading:18194215-Sp1 Transcription Factor, pubmed-meshheading:18194215-Synaptosomal-Associated Protein 25, pubmed-meshheading:18194215-Transcription, Genetic, pubmed-meshheading:18194215-Transcription Initiation Site, pubmed-meshheading:18194215-Transfection
pubmed:year
2008
pubmed:articleTitle
SP1 regulates a human SNAP-25 gene expression.
pubmed:affiliation
Department of Psychiatry, Brain Research Center, The University of British Columbia, Vancouver, British Columbia, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't