PMID: identifiant
de la référence Pubmed : |
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 (16723356) |
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| titre : |
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Distinct roles of the steroid receptor coactivator 1 and of MED1 in retinoid-induced transcription and cellular differentiation. |
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| auteur(s) : |
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Sébastien Flajollet1, 2, Bruno Lefebvre1, 2, Christophe Rachez3, Philippe Lefebvre1, 2 |
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| laboratoire : |
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| résumé : |
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Retinoic acid receptors (RARs) are the molecular relays of retinoid action on transcription, cellular differentiation and apoptosis. Transcriptional activation of retinoid-regulated promoters requires the dismissal of corepressors and the recruitment of coactivators to promoter-bound RAR. RARs recruit in vitro a plethora of coactivators whose actual contribution to retinoid-induced transcription is poorly characterized in vivo. Embryonal carcinoma P19 cells, which are highly sensitive to retinoids, were depleted from archetypical coactivators by RNAi. SRC1-deficient P19 cells showed severely compromised retinoid-induced responses, in agreement with the supposed role of SRC1 as a RAR coactivator. Unexpectedly, Med1/TRAP220/DRIP205-depleted cells exhibited an exacerbated response to retinoids, both in terms transcriptional responses and of cellular differentiation. Med1 depletion affected TFIIH and cdk9 detection at the prototypical retinoid-regulated RARbeta2 promoter, and favored a higher RNA polymerase II detection in transcribed regions of the RARbeta2 gene. Furthermore, the nature of the ligand impacted strongly on the ability of RARs to interact with a given coactivator and to activate transcription in intact cells. Thus RAR accomplishes transcriptional activation as a function of the ligand structure, by recruiting regulatory complexes which control distinct molecular events at retinoid-regulated promoters. |
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| domaine : |
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Sciences du Vivant/Médecine humaine et pathologie/Endocrinologie et métabolisme
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0021-9258 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1074/jbc.M603023200 |
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| journal : |
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J Biol Chem |
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| date de publication : |
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2006 |
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| volume : |
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281 |
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| page, identifiant, ... : |
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20338-48 |
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