Role of three SF-1 binding sites in the expression of the mvdp/akr1-b7 isocaproaldehyde reductase in Y1 cells.
Mvdp/akr1-b7 encodes an aldose-reductase-like enzyme expressed in the zona fasciculata of the adrenal cortex, the function of which is essential for the detoxification of the cholesterol side chain cleavage product, isocaproaldehyde. The -510/+41 akr1-b7 promoter fragment is able to reproduce the endogenous gene zona fasciculata restricted, ACTH-controlled expression, in transgenic mice adrenals. Here, we report that three response elements contained within this promoter (positions -102, -458, -503) are able to bind SF-1, the essential regulator of steroidogenesis, although the low affinity site at -503 retains some other specific proteins present in Y1 nuclear extracts. Mutation of the -102 site results in a lowering of the activity of the -510/+41 promoter in Y1 cells, whereas mutation of the -458 site induces a reduction both in the global activity and forskolin sensitivity of the promoter. Interestingly, differential mutations of the -503 site nucleotides either induce an increase or a decrease in the basal and forskolin-induced activity.
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UMR CNRS 6547, Physiologie Comparée et Endocrinologie Moléculaire, 24 Avenue des Landais, 63177 Aubiere, Cedex France.
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Lefrançois-Martinez
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Jean
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Veyssière
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Martinez
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D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism; D000449:Aldehyde Reductase; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins; D010446:Peptide Fragments / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology; D011506:Proteins / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D020218:Response Elements / Q000502:physiology; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D010446:Peptide Fragments; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C066498:Akr1b7 protein, mouse; D000449:Aldehyde Reductase