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Titolo:
MUTUALLY EXCLUSIVE INTERACTIONS OF 2 NUCLEAR ORPHAN RECEPTORS DETERMINE ACTIVITY OF A CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE-RESPONSIVE SEQUENCE IN THE BOVINE CYP17 GENE
Autore:
BAKKE M; LUND J;
Indirizzi:
KAROLINSKA INST,HUDDINGE UNIV HOSP,NOVUM M60,DEPT MED NUTR S-14186 HUDDINGE SWEDEN KAROLINSKA INST,HUDDINGE UNIV HOSP,NOVUM M60,DEPT MED NUTR S-14186 HUDDINGE SWEDEN
Titolo Testata:
Molecular endocrinology
fascicolo: 3, volume: 9, anno: 1995,
pagine: 327 - 339
SICI:
0888-8809(1995)9:3<327:MEIO2N>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROMOTER TRANSCRIPTION FACTOR; RETINOIC ACID RECEPTORS; STEROIDOGENIC FACTOR-I; THYROID-HORMONE; COUP-TF; ADRENOCORTICAL EXPRESSION; DEPENDENT TRANSCRIPTION; REGULATORY ELEMENTS; RESPONSIVE ELEMENT; PROTEIN-KINASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
53
Recensione:
Indirizzi per estratti:
Citazione:
M. Bakke e J. Lund, "MUTUALLY EXCLUSIVE INTERACTIONS OF 2 NUCLEAR ORPHAN RECEPTORS DETERMINE ACTIVITY OF A CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE-RESPONSIVE SEQUENCE IN THE BOVINE CYP17 GENE", Molecular endocrinology, 9(3), 1995, pp. 327-339

Abstract

ACTH-dependent transcriptional activation of the bovine CYP17 gene (the gene encoding cytochrome P450 steroid 17 alpha-hydroxylase) involves two cAMP-responsive sequences (CRS1 and CRS2) located in the promoter region. Here we demonstrate that two nuclear orphan receptors, chicken ovalbumin upstream promoter transcription factor (COUP-TF) and steroidogenic factor-1 (SF-1), bind to the part of the CRS2 element that contains the repeated sequences AAGTCA and AGGTCA spaced by six nucleotides (repCRS2). Overexpression of COUP-TF and SF-1 in both steroidogenic and nonsteroidogenic cells demonstrated that SF-1 is an activator of repCRS2-dependent transcription of reporter genes. Furthermore, the SF-1-dependent transcription could be further stimulated by activationof the cAMP-dependent protein kinase. In contrast, COUP-TF alone had no effect on repCRS2-dependent reporter gene activity. Mutations that interfere with the binding of SF-1 to repCRS2 in vitro abolished the cAMP-induced activities mediated by the element in transfected Y1 cells. The mutational analysis of repCRS2 further indicated that the binding sites for the two receptors overlap, and electrophoretic mobility shift assays demonstrated that the receptors bound in a mutually exclusive manner. Overexpression of both SF-1 and COUP-TFI simultaneously demonstrated that COUP-TFI inhibited SF-1-dependent activation of reporter genes. Transient transfection experiments with a construct containing a -100/+19 base pair fragment from the bovine CYP17 gene demonstrated that SF-1 and COUP-TF had similar effects on the intact promoter as on the repCRS2/reporter gene constructs. Our data suggest that the twoorphan receptors bind in a mutually exclusive manner to repCRS2 and that SF-1 is involved in the activation and COUP-TF in the repression of repCRS2-dependent transcription.

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Documento generato il 23/09/20 alle ore 22:16:18