| http://purl.uniprot.org/citations/7559606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/7559606 | http://www.w3.org/2000/01/rdf-schema#comment | "Insulin-like growth factor binding protein-5 (IG-FBP-5) is an important modulator of IGF actions. IG-FBP-5 mRNA is abundant in human fibroblasts and is regulated by cAMP. To understand the molecular mechanism underlying this cell type-specific expression and regulation, we isolated the 5'-flanking region of the human IGFBP-5 gene and fused it to a promoter-less reporter plasmid encoding luciferase. Transient transfection of the construct into fibroblasts displayed both constitutive and cAMP-induced promoter activity in an orientation-specific manner. Sequence analysis revealed the existence of distal and proximal consensus AP-2 recognition sites located 5' from the TATA box. Both sequences bound specifically to human AP-2 in vitro by gel shift mobility assay. The possible role of AP-2 was examined by cotransfection of AP-2-deficient HepG2 cells with the IGFBP-5 promoter construct and a human AP-2 expression construct. Cotransfection with AP-2 significantly elevated IGFBP-5 promoter activity. This trans-activation was IGFBP-5 promoter and AP-2 specific. In AP-2 abundant fibroblasts, expression of AP-2B, a dominant-negative inhibitor of AP-2, suppressed IGFBP-5 promoter activity. In HepG2 cells, AP-2B alone had no significant effect, but the AP-2-induced activation of promoter activity was inhibited by AP-2B in a dose-dependent manner. The relative functional importance of the putative AP-2 binding sites was examined using a number of deletion mutants and point mutations. When the first two distal CCCCACCC-like putative AP-2 sites were deleted or mutated, there was no change in AP-2-induced trans-activation. Deletion or mutation of the proximal GCCNNNGGC-like sequences, however, abolished the AP-2-induced activation. These results suggest that AP-2 regulates the IGFBP-5 gene expression through the proximal GCCNNNGGC-like sequences. This AP-2-mediated trans-activation contributes at least in part to the constitutively high expression of IGFBP-5 in fibroblasts and to the cAMP responsiveness of this gene."xsd:string |
| http://purl.uniprot.org/citations/7559606 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.270.42.24844"xsd:string |
| http://purl.uniprot.org/citations/7559606 | http://purl.uniprot.org/core/author | "Duan C."xsd:string |
| http://purl.uniprot.org/citations/7559606 | http://purl.uniprot.org/core/author | "Clemmons D.R."xsd:string |
| http://purl.uniprot.org/citations/7559606 | http://purl.uniprot.org/core/date | "1995"xsd:gYear |
| http://purl.uniprot.org/citations/7559606 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/7559606 | http://purl.uniprot.org/core/pages | "24844-24851"xsd:string |
| http://purl.uniprot.org/citations/7559606 | http://purl.uniprot.org/core/title | "Transcription factor AP-2 regulates human insulin-like growth factor binding protein-5 gene expression."xsd:string |
| http://purl.uniprot.org/citations/7559606 | http://purl.uniprot.org/core/volume | "270"xsd:string |
| http://purl.uniprot.org/citations/7559606 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/7559606 |
| http://purl.uniprot.org/citations/7559606 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/7559606 |
| http://purl.uniprot.org/uniprot/Q92481#attribution-1C440017229B4C2D51494A05C9673954 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/7559606 |
| http://purl.uniprot.org/uniprot/Q92481#attribution-8E0E44A1904F45FEC90B8D2E035BD485 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/7559606 |
| http://purl.uniprot.org/uniprot/P05549#attribution-8E0E44A1904F45FEC90B8D2E035BD485 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/7559606 |
| http://purl.uniprot.org/uniprot/P24593#attribution-8E0E44A1904F45FEC90B8D2E035BD485 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/7559606 |