| NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5. | |
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MedLine Citation:
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PMID: 19861119 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPARbeta/delta signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved in cross-regulatory control we decided to further investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression was up-regulated by Nurr1 and other NR4A NRs in HEK293 cells, and Nurr1 was shown to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPARbeta/delta and DHA-induced activation of RXR. We also found that other members of the NR4A orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs can influence signaling events of other NRs via control of FABP5 expression levels. |
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Authors:
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Nikolaos Volakakis; Eliza Joodmardi; Thomas Perlmann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-25 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 390 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-30 Completed Date: 2010-01-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 1186-91 Citation Subset: IM |
Affiliation:
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Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Cell Line Docosahexaenoic Acids / metabolism* Fatty Acid-Binding Proteins / genetics* Gene Expression Regulation* Humans Nuclear Receptor Subfamily 4, Group A, Member 2 / metabolism* PPAR gamma / metabolism PPAR-beta / metabolism Promoter Regions, Genetic Retinoid X Receptor alpha / metabolism Signal Transduction Transcription, Genetic Tretinoin / metabolism*, pharmacology Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/FABP5 protein, human; 0/Fatty Acid-Binding Proteins; 0/NR4A2 protein, human; 0/Nuclear Receptor Subfamily 4, Group A, Member 2; 0/PPAR gamma; 0/PPAR-beta; 0/Retinoid X Receptor alpha; 25167-62-8/Docosahexaenoic Acids; 302-79-4/Tretinoin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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