HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 29, 20338-20348, July 21, 2006

This Article Full Text Full Text (PDF) Supplemnetal Data Supplemental Data All Versions of this Article: 281/29/20338    most recent M603023200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Flajollet, S. Articles by Lefebvre, P. Search for Related Content PubMed PubMed Citation Articles by Flajollet, S. Articles by Lefebvre, P. Social Bookmarking                      What's this?

Distinct Roles of the Steroid Receptor Coactivator 1 and of MED1 in Retinoid-induced Transcription and Cellular Differentiation^*

From the INSERM U459, FacultédeMédecine Henri Warembourg, Lille F-59045, France

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 RAR2 promoter, and favored a higher RNA polymerase II detection in transcribed regions of the RAR2 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.

Received for publication, March 30, 2006 , and in revised form, May 23, 2006.

^* This work was supported by grants from INSERM and Ligue Nationale contre le Cancer and Comité du Nord de la Ligue Nationale contre le Cancer. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by fellowships from Région Nord Pas de Calais and INSERM, and from La Ligue Nationale contre le Cancer. Present address: Institut Pasteur de Lille, Département d'Athérosclérose, Lille, F-59019.

² Present address: Institut Pasteur de Lille, Département d'Athérosclérose, Lille, F-59019.

³ Present address: Unitéde Génétique de la Différenciation, URA 2578 du CNRS, Département de Biologie du Développement, Institut Pasteur, 75724 Paris Cedex 15, France.

⁴ To whom correspondence should be addressed: Facultéde Médecine de Lille, 1 place de Verdun, 59045 Lille cedex, France. Tel.: 33-3-20626876; Fax: 33-3-20626884; E-mail: p.lefebvre{at}lille.inserm.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Lefebvre, B. Cariou, F. Lien, F. Kuipers, and B. Staels Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation Physiol Rev, January 1, 2009; 89(1): 147 - 191. [Abstract] [Full Text] [PDF]

				N. K. Saxena, P. M. Vertino, F. A. Anania, and D. Sharma Leptin-induced Growth Stimulation of Breast Cancer Cells Involves Recruitment of Histone Acetyltransferases and Mediator Complex to CYCLIN D1 Promoter via Activation of Stat3 J. Biol. Chem., May 4, 2007; 282(18): 13316 - 13325. [Abstract] [Full Text] [PDF]