| pubmed-article:20060928 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20060928 | lifeskim:mentions | umls-concept:C0597298 | lld:lifeskim |
| pubmed-article:20060928 | lifeskim:mentions | umls-concept:C0441472 | lld:lifeskim |
| pubmed-article:20060928 | lifeskim:mentions | umls-concept:C0671771 | lld:lifeskim |
| pubmed-article:20060928 | lifeskim:mentions | umls-concept:C0015272 | lld:lifeskim |
| pubmed-article:20060928 | lifeskim:mentions | umls-concept:C0591833 | lld:lifeskim |
| pubmed-article:20060928 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:20060928 | pubmed:dateCreated | 2010-3-9 | lld:pubmed |
| pubmed-article:20060928 | pubmed:abstractText | The orphan nuclear receptor pregnane X receptor regulates enzymes and transport proteins involved in the detoxification and clearance of numerous endobiotic and xenobiotic compounds, including pharmaceutical agents. Multiple alternatively spliced pregnane X receptor isoforms have been identified which are significantly expressed in humans and mice (up to 30% of the total pregnane X receptor transcript), however, little is known about their biological action. We explored functional differences between the major mouse pregnane X receptor isoforms mPXR(431) and mPXR(Delta171-211) that lacks 41 amino acids adjacent to the ligand-binding pocket. Transient transfection assays showed that mPXR(Delta171-211) reduced the basal transcription of cytochrome P450 3A4 and the drug transporter P-glycoprotein/Multi Drug Resistance Protein 1 and directly repressed the regulatory effects of mPXR(431) on these genes. Replacement of the mPXR(Delta171-211) DNA-binding domain with that of GAL4 showed mPXR(Delta171-211) retained its repressive role independent of binding to PXR responsive elements located within the cytochrome P450 3A4 and Multi Drug Resistance Protein 1 regulatory regions. Use of the histone deacetylase inhibitor, trichostatin A, demonstrated that the repressive function of mPXR(Delta171-211) acts independently of histone acetylation state. Protein interaction assays revealed mPXR(Delta171-211) and mPXR(431) differentially bind the obligatory heterodimer partner retinoid X receptor. Furthermore, mPXR(431) and mPXR(Delta171-211) proteins could heterodimerize. These studies demonstrate that the variant mouse PXR isoform, mPXR(Delta171-211), has a distinct repressive function from mPXR(431) in regulating genes encoding important drug metabolizing enzymes and transport proteins. | lld:pubmed |
| pubmed-article:20060928 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20060928 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20060928 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20060928 | pubmed:month | May | lld:pubmed |
| pubmed-article:20060928 | pubmed:issn | 1878-5875 | lld:pubmed |
| pubmed-article:20060928 | pubmed:author | pubmed-author:YinY MYM | lld:pubmed |
| pubmed-article:20060928 | pubmed:author | pubmed-author:RobertsonGrah... | lld:pubmed |
| pubmed-article:20060928 | pubmed:author | pubmed-author:ClarkeStephen... | lld:pubmed |
| pubmed-article:20060928 | pubmed:author | pubmed-author:PollyPatsieP | lld:pubmed |
| pubmed-article:20060928 | pubmed:author | pubmed-author:TsoliMariaM | lld:pubmed |
| pubmed-article:20060928 | pubmed:author | pubmed-author:CorradinAntho... | lld:pubmed |
| pubmed-article:20060928 | pubmed:copyrightInfo | 2010 Elsevier Ltd. All rights reserved. | lld:pubmed |
| pubmed-article:20060928 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20060928 | pubmed:volume | 42 | lld:pubmed |
| pubmed-article:20060928 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20060928 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20060928 | pubmed:pagination | 672-82 | lld:pubmed |
| pubmed-article:20060928 | pubmed:meshHeading | pubmed-meshheading:20060928... | lld:pubmed |
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| pubmed-article:20060928 | pubmed:meshHeading | pubmed-meshheading:20060928... | lld:pubmed |
| pubmed-article:20060928 | pubmed:meshHeading | pubmed-meshheading:20060928... | lld:pubmed |
| pubmed-article:20060928 | pubmed:meshHeading | pubmed-meshheading:20060928... | lld:pubmed |
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| pubmed-article:20060928 | pubmed:meshHeading | pubmed-meshheading:20060928... | lld:pubmed |
| pubmed-article:20060928 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20060928 | pubmed:articleTitle | The alternatively spliced murine pregnane X receptor isoform, mPXR(delta171-211) exhibits a repressive action. | lld:pubmed |
| pubmed-article:20060928 | pubmed:affiliation | Cancer Pharmacology Unit, ANZAC Research Institute, Hospital Road, Concord RG Hospital, NSW 2139, Australia. mmatic@med.usyd.edu.au | lld:pubmed |
| pubmed-article:20060928 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20060928 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:20060928 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:18171 | entrezgene:pubmed | pubmed-article:20060928 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:20060928 | lld:entrezgene |
