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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2011-4-11
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pubmed:abstractText |
Glucocorticoid-induced apoptosis of thymocytes is one of the first recognized forms of programmed cell death. It was shown to require gene activation induced by the glucocorticoid receptor (GR) translocated into the nucleus following ligand binding. In addition, the necessity of the glucocorticoid-induced, but transcription-independent phosphorylation of phosphatidylinositol-specific phospholipase C (PI-PLC) has also been shown. Here we report that retinoic acids, physiological ligands for the nuclear retinoid receptors, enhance glucocorticoid-induced death of mouse thymocytes both in vitro and in vivo. The effect is mediated by retinoic acid receptor (RAR) alpha/retinoid X receptor (RXR) heterodimers, and occurs when both RAR? and RXR are ligated by retinoic acids. We show that the ligated RAR?/RXR interacts with the ligated GR, resulting in an enhanced transcriptional activity of the GR. The mechanism through which this interaction promotes GR-mediated transcription does not require DNA binding of the retinoid receptors and does not alter the phosphorylation status of Ser232, known to regulate the transcriptional activity of GR. Phosphorylation of PI-PLC was not affected. Besides thymocytes, retinoids also promoted glucocorticoid-induced apoptosis of various T-cell lines, suggesting that they could be used in the therapy of glucocorticoid-sensitive T-cell malignancies.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Dsip1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/LG 268,
http://linkedlifedata.com/resource/pubmed/chemical/Organic Chemicals,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoinositide Phospholipase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoid X Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/alitretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor alpha
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1476-5403
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
783-92
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pubmed:meshHeading |
pubmed-meshheading:21072052-Animals,
pubmed-meshheading:21072052-Apoptosis,
pubmed-meshheading:21072052-Cells, Cultured,
pubmed-meshheading:21072052-DNA Fragmentation,
pubmed-meshheading:21072052-Dexamethasone,
pubmed-meshheading:21072052-Gene Deletion,
pubmed-meshheading:21072052-Glucocorticoids,
pubmed-meshheading:21072052-Humans,
pubmed-meshheading:21072052-Immunoprecipitation,
pubmed-meshheading:21072052-Male,
pubmed-meshheading:21072052-Mice,
pubmed-meshheading:21072052-Mice, Inbred BALB C,
pubmed-meshheading:21072052-Mice, Knockout,
pubmed-meshheading:21072052-Organic Chemicals,
pubmed-meshheading:21072052-Phosphoinositide Phospholipase C,
pubmed-meshheading:21072052-Phosphorylation,
pubmed-meshheading:21072052-Protein Multimerization,
pubmed-meshheading:21072052-Receptors, Glucocorticoid,
pubmed-meshheading:21072052-Receptors, Retinoic Acid,
pubmed-meshheading:21072052-Retinoid X Receptors,
pubmed-meshheading:21072052-Retinoids,
pubmed-meshheading:21072052-T-Lymphocytes,
pubmed-meshheading:21072052-Transcription, Genetic,
pubmed-meshheading:21072052-Transcription Factors,
pubmed-meshheading:21072052-Transcriptional Activation,
pubmed-meshheading:21072052-Tretinoin,
pubmed-meshheading:21072052-Two-Hybrid System Techniques
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pubmed:year |
2011
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pubmed:articleTitle |
Retinoids enhance glucocorticoid-induced apoptosis of T cells by facilitating glucocorticoid receptor-mediated transcription.
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pubmed:affiliation |
Apoptosis and Genomics Research Group, Department of Biochemistry and Molecular Biology, Hungarian Academy of Sciences, University of Debrecen, Nagyerdei krt. 98, Debrecen, Hungary.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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