http://purl.uniprot.org/citations/15123650 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/15123650 | http://www.w3.org/2000/01/rdf-schema#comment | "Small heterodimer partner (SHP; NR0B2) is an unusual orphan nuclear receptor that lacks a conventional DNA-binding domain and acts as a modulator of transcriptional activities of a number of nuclear receptors. Herein, we report that the human SHP promoter (hSHP) is activated by sterol regulatory element-binding protein-1 (SREBP-1), which regulates the expression of various genes involved in cholesterol and fatty acid synthesis. Overexpression of SREBP-1 activated the human but not mouse SHP promoter, although SREBP-2 had little effect on the SHP promoter in CV-1 cells. Serial deletion reporter assays revealed that SREBP-1-responsive region is located within the sequences from -243 to -120 bp in the hSHP promoter. DNase I footprinting, gel shift assays, and chromatin immunoprecipitation assays demonstrated that SREBP-1 binds directly to the hSHP promoter. Site-directed mutagenesis made it clear that the hSHP promoter activation by SREBP-1 is mostly mediated by the SRE1 (-186 to -195 bp) in the hSHP promoter, which is not conserved in the mouse SHP promoter. Moreover, adenovirus-mediated overexpression of SREBP-1c/ADD-1 induced SHP mRNA expression and repressed CYP7A1 expression in HepG2 cells. Finally, we found that a four-nucleotide deletion (-195CT-GAdel) in the hSHP promoter, which is reported to be associated with altered body weight and insulin secretion in human, coincides with the SRE1. This mutation strongly decreased both basal and SREBP-1 dependent activities of the hSHP promoter, because of the reduced binding of SREBP-1 to the mutated SRE1. Overall, our results demonstrate a differential regulation of human and mouse SHP promoters by SREBP-1. We propose a possible role of SREBP-1 in the species differential regulation of cholesterol and bile acid homeostasis via a novel mechanism of up-regulation of the hSHP gene expression."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m313302200"xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Kim H.J."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Kim K.S."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Lee I.K."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Kim J.Y."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Park S.K."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Seo J.H."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Choi H.S."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Kim J.B."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/author | "Kim J.Y.'"xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/pages | "28122-28131"xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/title | "Differential regulation of human and mouse orphan nuclear receptor small heterodimer partner promoter by sterol regulatory element binding protein-1."xsd:string |
http://purl.uniprot.org/citations/15123650 | http://purl.uniprot.org/core/volume | "279"xsd:string |
http://purl.uniprot.org/citations/15123650 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15123650 |
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