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Titolo:
Conditional response of the human steroidogenic acute regulatory protein gene promoter to sterol regulatory element binding protein-1a
Autore:
Christenson, LK; Osborne, TF; McAllister, JM; Strauss, JF;
Indirizzi:
Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 mens Hlth, Philadelphia, PA 19104 USA Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA Univ Calif Irvine Irvine CA USA 92717 iol & Biochem, Irvine, CA 92717 USA Penn State Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA Penn State Coll Med Hershey PA USA 17033 l Physiol, Hershey, PA 17033 USA
Titolo Testata:
ENDOCRINOLOGY
fascicolo: 1, volume: 142, anno: 2001,
pagine: 28 - 36
SICI:
0013-7227(200101)142:1<28:CROTHS>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIPOPROTEIN RECEPTOR GENE; LEUCINE ZIPPER PROTEIN; HUMAN GRANULOSA-CELLS; TRANSCRIPTION FACTOR; STAR GENE; CHOLESTERYL ESTER; EXPRESSION; YY1; COENZYME; BIOSYNTHESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Christenson, LK 1354 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA 1354 BRB 2-3,421 Curie Blvd Philadelphia PA USA 19104 USA
Citazione:
L.K. Christenson et al., "Conditional response of the human steroidogenic acute regulatory protein gene promoter to sterol regulatory element binding protein-1a", ENDOCRINOL, 142(1), 2001, pp. 28-36

Abstract

The steroidogenic acute regulatory protein (StAR) gene controls the rate-limiting step in the biogenesis of steroid hormones, delivery of cholesterolto the cholesterol side-chain cleavage enzyme on the inner mitochondrial membrane. We determined whether the human StAR promoter is responsive to sterol regulatory element-binding proteins (SREBPs). Expression of SREBP-1a stimulated StAR promoter activity in the context of COS-1 cells and human granulosalutein cells. In contrast, expression of SREBP-8 produced only a modest stimulation of StAR promoter activity. One of the SREBP-1a response elements in the StAR promoter was mapped in deletion constructs and by site-directed mutagenesis between nucleotides -81 to -70 from the transcription start site. This motif bound recombinant SREBPs in electrophoretic mobility shift assays, but with lesser affinity than a low density lipoprotein receptor SREBP-binding site. An additional binding site for the transcriptional modulator, yin yang 1 (YY1), was observed within the SREBP-binding site (nucleotides -73 to -70). Mutation of the YY1-binding site increased the responsiveness of the StAR promoter to exogenous SREBP-1a, but did not alter the affinity for SREBP-1a binding in electrophoretic mobility gel shift assays. Manipulations that altered endogenous mature SREBP-1a levels (e.g. culture in lipoprotein-deficient medium and addition of 27-hydroxycholesterol) did not affect StAR promoter function, but influenced low density lipoprotein receptor promoter activity. We conclude that 1) the human StAR promoter is conditionally responsive to SREBP-1a such that promoter activity is up-regulated in the presence of high levels of SREBP-1a, but is unaffected when mature SREBP levels are suppressed; and 2) the human StAR promoter is selectively responsive to SREBP-1a.

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Documento generato il 29/09/20 alle ore 06:34:12