Linked Life Data

9651314

Source:http://linkedlifedata.com/resource/pubmed/id/9651314

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
1998-8-6
pubmed:databankReference
pubmed:abstractText
Several lines of evidence suggest a role for laminin-5 in skin wound healing. We report here that transforming growth factor-beta (TGF-beta), which elicits various responses during cutaneous healing, stimulates transcription of the mouse laminin alpha3A (lama3A) gene. To identify the TGF-beta-responsive elements (TGFbeta-REs) on the lama3A promoter, we have generated a series of 5'-deletions of the promoter upstream of the beta-galactosidase reporter gene. Transient cell transfection assays using mouse PAM212 keratinocytes revealed that TGFbeta-REs lie between nucleotides -297 and -54 relative to the transcription start site. Insertion of the TGFbeta-RE in front of the unresponsive minimal SV40 promoter conferred TGF-beta inducibility. Computer analysis of the promoter sequence identified three canonical activator protein-1 (AP-1) sites located at nucleotides -277 (AP-1A), -125 (AP-1B), and -69 (AP-1C). Site-directed mutagenesis of either the AP-1A or AP-1C site did not drastically alter the basal activity of the lama3A promoter, but reduced TGF-beta responsiveness by 50%. Simultaneous mutation of these two AP-1 sites resulted in a 65% decline in the response to TGF-beta, suggesting a cooperative contribution of each site to the overall promoter activity. In contrast, mutation of the AP-1B site markedly reduced the basal activity of the lama3A promoter, indicating that this AP-1 site is essential for gene expression. Mobility shift assays demonstrated specific binding of Fra-2 and JunD to the AP-1 sites, suggesting for the first time a possible regulatory function for the Fra-2.JunD AP-1 complex in a basal keratinocyte-specific gene.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17318-25
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Three activator protein-1-binding sites bound by the Fra-2.JunD complex cooperate for the regulation of murine laminin alpha3A (lama3A) promoter activity by transforming growth factor-beta.
pubmed:affiliation
INSERM U385, Faculté de Médecine, 06107 Nice Cedex 2, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't