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Titolo:
AR suppresses transcription of the alpha glycoprotein hormone subunit genethrough protein-protein interactions with cJun and activation transcription factor 2
Autore:
Jorgensen, JS; Nilson, JH;
Indirizzi:
Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA Case Western Reserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 9, volume: 15, anno: 2001,
pagine: 1496 - 1504
SICI:
0888-8809(200109)15:9<1496:ASTOTA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN ANDROGEN RECEPTOR; ESTROGEN-RECEPTOR; C-JUN; DNA-BINDING; GLUCOCORTICOID RECEPTOR; HISTONE DEACETYLASE; PROXIMAL PROMOTER; TRANSGENIC MICE; LIGAND-BINDING; 26S PROTEASOME;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Nilson, JH Case Western Reserve Univ, Sch Med, Dept Pharmacol, W319,2109 Adelbert Rd,Cleveland, OH 44106 USA Case Western Reserve Univ W319,2109 Adelbert Rd Cleveland OH USA 44106
Citazione:
J.S. Jorgensen e J.H. Nilson, "AR suppresses transcription of the alpha glycoprotein hormone subunit genethrough protein-protein interactions with cJun and activation transcription factor 2", MOL ENDOCR, 15(9), 2001, pp. 1496-1504

Abstract

Previously, we reported that the AR directly suppressed transcription of the a glycoprotein hormone subunit (alpha GSU) gene in a ligand-dependent fashion while ER had no effect. Mutagenesis studies of the alpha GSU promoterindicated that two elements were required for AR-mediated suppression: thea basal element and tandem cAMP response elements (CREs). Because several members of the bZip family of transcriptional proteins can bind the CREs, we used several functional assays to determine whether AR interacts selectively with cJun, activation transcription factor 2 (ATF2), or CRE binding protein (CREB). When tested by cotransfection with AR, cJun and ATF2 specifically rescued androgen-mediated suppression of the alpha GSU-reporter construct in a gonadotrope-derived cell line. In contrast, cotransfected CREB displayed no activity in this rescue assay. In fact, overexpression of CREB alone diminished activity of the alpha GSU promoter, suggesting that the transcriptional activity normally conferred by the tandem CREs in gonadotropes requires their occupancy by cJun/ATF2 heterodimers. Binding assays carried out with a glutathione-S-transferase-AR fusion protein indicated that the receptor itself also displayed a clear preference for binding cJun and ATF2. Furthermore, we ruled out the possibility that AR suppressed activity of the alpha GSU promoter by reducing synthesis of these bZip proteins. Additional experiments suggested that phosphorylation of AR or histone acetylation are unlikely requirements for AR suppression of alpha GSU promoter activity. Thus, our data suggest that AR suppresses activity of the alpha GSU promoter through direct protein-protein interactions with cJun and ATF2.

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Documento generato il 25/01/20 alle ore 18:45:42