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Titolo:
DETERMINANTS OF PROMOTER-SPECIFIC ACTIVITY BY GLUCOCORTICOID RECEPTOR
Autore:
GUIDO EC; DELORME EO; CLEMM DL; STEIN RB; ROSEN J; MINER JN;
Indirizzi:
LIGAND PHARMACEUT INC,TRANSCRIPT RES DEPT,10255 SCI CTR DR SAN DIEGO CA 92121 LIGAND PHARMACEUT INC,TRANSCRIPT RES DEPT SAN DIEGO CA 92121 LIGAND PHARMACEUT INC,DEPT ENDOCRINE RES SAN DIEGO CA 92121
Titolo Testata:
Molecular endocrinology
fascicolo: 10, volume: 10, anno: 1996,
pagine: 1178 - 1190
SICI:
0888-8809(1996)10:10<1178:DOPABG>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN ESTROGEN-RECEPTOR; PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; HUMAN PROGESTERONE-RECEPTOR; TUMOR VIRUS PROMOTER; DNA-BINDING; CONFORMATIONAL-CHANGES; IN-VIVO; C-JUN; TRANSCRIPTION; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
E.C. Guido et al., "DETERMINANTS OF PROMOTER-SPECIFIC ACTIVITY BY GLUCOCORTICOID RECEPTOR", Molecular endocrinology, 10(10), 1996, pp. 1178-1190

Abstract

Glucocorticoid receptor (GR) is expressed at essentially equal levelsin almost ail tissues and cell types. Remarkably, glucocorticoids themselves regulate transcription in vivo in both a promoter- and tissue-specific manner. Thus, specific systems must be in place to regulate receptor action within certain cells and at certain promoters. To address two specific aspects of these systems, we have analyzed promoter-specific activity of GR using two different, well studied promoters (termed simple and composite promoters) from which GR activates transcription. The simple promoter depends only on the receptor for glucocorticoid-responsive transcriptional activation, while GR activity at the composite promoter depends on additional transcription factors. We have compared the action of several GR ligands at these promoters end demonstrate fundamental differences in the activities of these ligands on receptor activity. Furthermore, these compounds induce unique conformational changes in receptor, resulting in promoter-specific receptor function. We have identified critical amino acid residues within GR which,when mutated, genetically distinguish the action of GR at these promoters. Taken together, the data indicate that the presence of only the receptor and the ligand is not sufficient to allow activation of transcription. An additional system of regulation influences receptor action in both a tissue- and promoter-selective fashion, suggesting that multiple, regulated surfaces of the receptor respond to the cellular environment and determine the spectrum of GR activities. These functionalsurfaces may be induced or regulated by ligand binding, by the DNA sequence to which receptor is bound, or by the nonreceptor factors resident at the promoter or in the tissue.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 12:30:15