Source:http://linkedlifedata.com/resource/pubmed/id/11095974
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2000-12-12
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pubmed:abstractText |
The transcriptional activator protein-2 (AP-2) has been suggested to participate in keratinocyte gene regulation. Cystatin A, a cysteine proteinase inhibitor, is one of the cornified cell envelope constituents and is expressed in the upper epidermis. We report AP-2-dependent transcriptional regulation of cystatin A gene expression of keratinocytes. At least three isoforms of AP-2 (AP-2 alpha, beta, gamma) have been described. Transfection of AP-2alpha, beta and gamma expression vectors into cultured normal human keratinocytes (NHK) resulted in increased cystatin A expression in both mRNA and protein levels. Among the three isoforms AP-2gamma was most potent in inducing cystatin A expression. In contrast, transfection of antisense oriented AP-2gamma expression vector decreased basal AP-2 expression, accompanied by decreased cystatin A mRNA. The fragment, +77 to -478 of 5'-flanking region of human cystatin A gene, was subcloned into chloramphenicol acetyltransferase (CAT) reporter vector (p478CAT). Cotransfection of p478CAT vector with AP-2alpha, beta, and gamma expression vectors resulted in three-, three-, and sixfold increase in the CAT activity, respectively. Transfection of the deleted construct (p478DeltaAP-2CAT, devoid of AP-2-like binding site (-75 to -84)) decreased CAT activity by one-third compared to p478CAT promoter activity. Cotransfection of p478DeltaAP-2CAT with AP-2alpha, beta, and gamma expression vectors had no effect on the decreased promoter activity. Immunohistochemical analysis of human skin showed that AP-2alpha is exclusively expressed in the nuclei of basal cell layer. AP-2gamma is expressed in the nuclei of basal, spinous, and granular cell layers. AP-2beta expression was not observed in the epidermis. Gel mobility shift assay revealed that the AP-2gamma protein specifically binds to oligonucleotides containing AP-2-like binding site of cystatin A gene. These results indicate that AP-2gamma regulates the cystatin A gene expression of epidermal keratinocytes at the transcriptional level.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Cystatins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/TFAP2A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TFAP2B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TFAP2C protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-2,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
719-23
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11095974-5' Untranslated Regions,
pubmed-meshheading:11095974-Amino Acid Sequence,
pubmed-meshheading:11095974-Base Sequence,
pubmed-meshheading:11095974-Cells, Cultured,
pubmed-meshheading:11095974-Cystatins,
pubmed-meshheading:11095974-DNA-Binding Proteins,
pubmed-meshheading:11095974-Gene Expression Regulation,
pubmed-meshheading:11095974-Humans,
pubmed-meshheading:11095974-Keratinocytes,
pubmed-meshheading:11095974-Molecular Sequence Data,
pubmed-meshheading:11095974-Protein Isoforms,
pubmed-meshheading:11095974-RNA, Messenger,
pubmed-meshheading:11095974-Transcription, Genetic,
pubmed-meshheading:11095974-Transcription Factor AP-2,
pubmed-meshheading:11095974-Transcription Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Transcriptional factor AP-2gamma increases human cystatin A gene transcription of keratinocytes.
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pubmed:affiliation |
Department of Dermatology, Asahikawa Medical College, Asahikawa, 078-8510, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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