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• W2167280914 endingPage "2132" @default.
• W2167280914 startingPage "2118" @default.
• W2167280914 abstract "Migration of cells requires interactions with the extracellular matrix mediated, in part, by integrins, proteases, and their receptors. Previous studies have shown that beta(3)-integrin interacts with the urokinase-type plasminogen activator receptor (u-PAR) at the cell surface. Since integrins mediate signaling into the cell, the current study was undertaken to determine if in addition beta(3)-integrin regulates u-PAR expression. Overexpression of beta(3)-integrin in CHO cells, which are avid expressers of the receptor, downregulated u-PAR protein and mRNA expression. The u-PAR promoter (-1,469 bp) that is normally constitutively active in CHO cells was downregulated by induced beta(3)-integrin expression. A region between -398 and -197 bp of the u-PAR promoter was critical for beta(3)-integrin-induced downregulation of u-PAR promoter activity. Deletion of the PEA3/ets motif at -248 bp substantially impaired the ability of beta(3)-integrin to downregulate the u-PAR promoter, suggesting that the PEA3/ets site acts as a silencing element. An expression vector encoding the transcription factor PEA3 caused inhibition of the wild-type but not the PEA3/ets-deleted u-PAR promoter. The PEA3/ets site bound nuclear factors from CHO cells specifically, but binding was enhanced when beta(3)-integrin was overexpressed. A PEA3 antibody inhibited DNA-protein complex formation, indicating the presence of PEA3. Downregulation of the u-PAR promoter was achieved by the beta(3)A-integrin isoform but not by other beta(3)-integrin isoforms and required the cytoplasmic membrane NITY(759) motif. Moreover, overexpression of the short but not the long isoform of the beta(3)-integrin adapter protein beta(3)-endonexin blocked u-PAR promoter activity through the PEA3/ets binding site. Thus, besides the physical interaction of beta(3)-integrin and u-PAR at the cell surface, beta(3) signaling is implicated in the regulation of u-PAR gene transcription, suggesting a mutual regulation of adhesion and proteolysis receptors." @default.
• W2167280914 created "2016-06-24" @default.
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• W2167280914 date "2001-03-01" @default.
• W2167280914 modified "2023-09-23" @default.
• W2167280914 title "β₃A-Integrin Downregulates the Urokinase-Type Plasminogen Activator Receptor (u-PAR) through a<i>PEA3/ets</i> Transcriptional Silencing Element in the u-PAR Promoter" @default.
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• W2167280914 doi "https://doi.org/10.1128/mcb.21.6.2118-2132.2001" @default.
• W2167280914 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/86830" @default.
• W2167280914 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11238946" @default.
• W2167280914 hasPublicationYear "2001" @default.
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