| pubmed-article:15372465 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15372465 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:15372465 | lifeskim:mentions | umls-concept:C0022567 | lld:lifeskim |
| pubmed-article:15372465 | lifeskim:mentions | umls-concept:C0221920 | lld:lifeskim |
| pubmed-article:15372465 | lifeskim:mentions | umls-concept:C0030190 | lld:lifeskim |
| pubmed-article:15372465 | lifeskim:mentions | umls-concept:C0076925 | lld:lifeskim |
| pubmed-article:15372465 | lifeskim:mentions | umls-concept:C0040649 | lld:lifeskim |
| pubmed-article:15372465 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:15372465 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:15372465 | pubmed:dateCreated | 2005-2-1 | lld:pubmed |
| pubmed-article:15372465 | pubmed:abstractText | Certain growth factors (e.g., TGF-beta1) initiate a "plastic" response in human keratinocytes (HaCaT cells) characterized by changes in gene expression and increased cell motility. While microarray analyses identified a number of involved genes, plasminogen activator inhibitor type 1 (PAI-1) is among the subset most highly responsive to TGF-beta1. Previous antisense attenuation of PAI-1 synthesis confirmed an essential role for this protease inhibitor in cell motility (Providence et al., 2002, J Cell Sci 115:3767-3777; Providence and Higgins, 2004, J Cell Physiol 200:297-308). It was important, therefore, to clarify molecular mechanisms underlying PAI-1 expression control in human keratinocytes. A consensus E box motif (5'-CACGTG-3') at nucleotides -566 to -561 in the PE2 region of the PAI-1 gene was required for TGF-beta1-induced transcription of a PAI-1 promoter-driven luceriferase reporter. Truncation of the PE2 E box or mutation of the CACGTG hexanucleotide to CAATTG inhibited growth factor-stimulated promoter function confirming the importance of this site in inducible expression. A similar mutation at the PE1 E box (nucleotides -682 to -677), in contrast, did not result in reduced luciferase activity. Competing CACGTG-containing DNAs, regardless of the presence or absence of PAI-1-specific flanking sequences or lacking accessory sequences (i.e., Smad-binding sites, AAT trinucleotide spacer), inhibited complex formation between HaCaT cell nuclear factors and a 45-mer PE2 region probe. A deoxyoligonucleotide that differed from the consensus E box by a CG --> AT substitution (the same base change incorporated into the PAI-1p806-lucerifase reporter by site-directed mutagenesis) but with random (i.e., non-PAI-1) flanking sequences also failed to compete with the PE2 region probe for protein binding whereas the same construct with an intact CACGTG motif was an effective competitor. The major protein/DNA interactions in the PE2 segment, therefore, are E box-dependent. USF-1, a member of the upstream stimulatory factor family, bound the PE2 construct suggesting a role for USF proteins in E box residence and PAI-1 gene expression. Chromatin immunoprecipitation, using primers designed to amplify a 300-bp PE2-associated promoter fragment and containing no other E box motifs except the target CACGTG at nucleotides -566 to -561, confirmed that this site was occupied by USF-1 or a USF-1-containing complex in both quiescent and TGF-beta1-stimulated cells. Transfection of a dominant-negative USF construct effectively attenuated serum- and TGF-beta1-induced PAI-1 synthesis as well as TGF-beta1-stimulated Matrigel barrier invasion. Dominant-negative USF-expressing keratinocytes, moreover, specifically had a reduced capacity for Matrigel barrier invasion. USF elements, therefore, are important regulators of growth factor-initiated PAI-1 transcription (as predicted from the identification of PAI-1 as a direct USF target gene) and the associated epithelial migratory response. | lld:pubmed |
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| pubmed-article:15372465 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15372465 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15372465 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15372465 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15372465 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:15372465 | pubmed:issn | 0021-9541 | lld:pubmed |
| pubmed-article:15372465 | pubmed:author | pubmed-author:HigginsPaul... | lld:pubmed |
| pubmed-article:15372465 | pubmed:author | pubmed-author:CHUE PEP | lld:pubmed |
| pubmed-article:15372465 | pubmed:author | pubmed-author:AllenRosalie... | lld:pubmed |
| pubmed-article:15372465 | pubmed:copyrightInfo | 2004 Wiley-Liss, Inc. | lld:pubmed |
| pubmed-article:15372465 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15372465 | pubmed:volume | 203 | lld:pubmed |
| pubmed-article:15372465 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15372465 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15372465 | pubmed:pagination | 156-65 | lld:pubmed |
| pubmed-article:15372465 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
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| pubmed-article:15372465 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15372465 | pubmed:articleTitle | Upstream stimulatory factor regulates E box-dependent PAI-1 transcription in human epidermal keratinocytes. | lld:pubmed |
| pubmed-article:15372465 | pubmed:affiliation | Center for Cell Biology & Cancer Research, Albany Medical College, Albany, New York 12208, USA. | lld:pubmed |
| pubmed-article:15372465 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15372465 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:15372465 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
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