| http://purl.uniprot.org/citations/15764585 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15764585 | http://www.w3.org/2000/01/rdf-schema#comment | "Activating signal cointegrator-2 (ASC-2) is a recently isolated transcriptional coactivator protein for a variety of different transcription factors, including many members of the nuclear receptor superfamily. In this report, we demonstrate that ASC-2 also serves as a coactivator of the xenobiotic nuclear receptor constitutive androstane receptor (CAR). First, transcriptional activation by CAR was enhanced by cotransfected ASC-2 in CV-1 and HeLa cells. In contrast, CAR transactivation was significantly impaired in HepG2 cells stably expressing specific small interfering RNA directed against ASC-2. Consistent with these results, chromatin immunoprecipitation experiments revealed that ASC-2 is recruited to the known CAR target genes in a ligand-dependent manner. Secondly, CAR specifically interacted with the first LXXLL motif of ASC-2, and these interactions were stimulated by CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene and repressed by CAR inverse agonist androstanol, suggesting that this motif may mediate the interactions of ASC-2 and CAR in vivo. In support of this idea, DN1, a fragment of ASC-2 encompassing the first LXXLL motif, suppressed CAR transactivation, and coexpressed ASC-2 but not other LXXLL-type coactivators such as thyroid hormone receptor-associated protein 220 reversed this repression. Finally, CAR was recently found to play a pivotal role in effecting the severe acetaminophen-induced liver damage. Interestingly, transgenic mice expressing DN1 were resistant to the acetaminophen-induced hepatotoxicity and expression of a series of the known CAR target genes was specifically repressed in these transgenic mice. Taken together, these results strongly suggest that ASC-2 is a bona fide coactivator of the xenobiotic nuclear receptor CAR and mediate the specific xenobiotic response by CAR in vivo."xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.org/dc/terms/identifier | "doi:10.1210/me.2005-0066"xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/author | "Lee S."xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/author | "Lee J.W."xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/author | "Kim S.W."xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/author | "Choi E."xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/author | "Kim G.H."xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/author | "Yeom S.Y."xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/name | "Mol Endocrinol"xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/pages | "1711-1719"xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/title | "Characterization of activating signal cointegrator-2 as a novel transcriptional coactivator of the xenobiotic nuclear receptor constitutive androstane receptor."xsd:string |
| http://purl.uniprot.org/citations/15764585 | http://purl.uniprot.org/core/volume | "19"xsd:string |
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