The Transcriptional Regulating Protein of 132 kDa (TReP-132) Enhances P450scc Gene Transcription through Interaction with Steroidogenic Factor-1 in Human Adrenal Cells

Gizard, Florence; Lavallée, Bernard; Dewitte, Frédérique; Teissier, Elisabeth; Staels, Bart; Hum, Dean W.

doi:10.1074/jbc.m205786200

Cited by 53 publications

(34 citation statements)

References 103 publications

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“…It appears that the recruitment of specific coregulators by zebra fish Ff1b might be required for the induction and specification of the interrenal organ. Besides the well-characterized interactions with DAX-1 and WT-1 (12,47), many other transcriptional activators like Egr-1, Ptx1, GATA4, USF, TReP-132, DEAD box protein DP103, and SOX9 could functionally modulate SF-1 (13,17,26,36,51,64,65,72,73). In gonadotrophs, for instance, Egr-1 synergizes with SF-1 to regulate the ␤ subunit of lutenizing hormone while Ptx1 acts in concert with SF-1 and Pit1 to regulate the Lim-homeodomain gene, Lim3/Lhx3 (36,72).…”

Section: Discussionmentioning

confidence: 99%

Prox1 Is a Novel Coregulator of Ff1b and Is Involved in the Embryonic Development of the Zebra Fish Interrenal Primordium

Liu

Gao

Teh

et al. 2003

Molecular and Cellular Biology

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Steroidogenic factor 1 (SF-1) plays an essential role in adrenal development, although the exact molecular mechanisms are unclear. Our previous work established that Ff1b is the zebra fish homologue of SF-1 and that its disruption by antisense morpholinos leads to a complete ablation of the interrenal organ. In this study, results of biochemical analyses suggest that Ff1b and other Ff1 members interact with Prox1, a homeodomain protein. Fine mapping using site-directed mutants showed that this interaction requires an intact Ff1b heptad 9 and AF2, as well as Prox1 NR Box I. In vivo, this physical interaction led to the inhibition of Ff1-mediated transactivation of pLuc3XFRE, indicating that Prox1 acts to repress the transcriptional activity of Ff1b. In situ hybridization demonstrates that prox1 colocalizes with ff1a and ff1b in the liver and interrenal primordia, respectively. Embryos microinjected with prox1 morpholino displayed a consistent partial reduction of 3␤-Hsd activity in the interrenal organ, while ff1b morpholino led to a disappearance of prox1. Based on these results, we propose that during the course of interrenal organogenesis, Prox1 functions as a tissue-specific coregulator of Ff1b and that the subsequent inhibition of Ff1b activity, after its initial roles in the specification of interrenal primordium, is critical for the maturation of the interrenal organ.Molecular and genetic evidence from experiments with mammals suggests that steroidogenic factor 1 (SF-1), dosagesensitive sex reversal-adrenal hypoplasia congenita critical region on the X-chromosome gene 1 (DAX-1), and Wilms' tumor 1 (WT-1) are absolutely required for the development of the adrenal cortex (32,52,53). They are expressed in the fetal adrenal at the earliest stages and appear to act in a concerted manner, probably by activating common development pathways to direct normal adrenal development (32, 53). SF-1, an orphan nuclear receptor (NR) with no known ligand, is expressed in the earliest precursors of the adrenal gland, the adrenogonadal progenitor cells (25,32), and SF-1 Ϫ/Ϫ knockout mice lack the adrenal gland (42, 59, 66). As a key regulator of adrenal development, it regulates the transcription of a number of genes involved in gonadal and adrenal development, including DAX-1 and MIS, and many of the enzymes involved in the steroidogenic pathway (25,30,47,53,64).WT-1 encodes a Kruppel-type zinc finger transcription factor (7, 16), and mutations of this gene in humans lead to congenital abnormalities of urogenital development (21). Experiments with knockout mice confirmed the importance of WT-1, which is expressed only in the adrenogonadal precursors but not in the fetal adrenal, since mice homozygous for a null allele lacked kidneys, gonads, and adrenals (35, 45). DAX-1 encodes a highly divergent orphan nuclear receptor (82). Although knockout mice lacking DAX-1 do not exhibit adrenocortical deficiency and show apparently normal development of the adrenal cortex, the expression of Cyp11A1 in the zona fasciculata is reduced (...

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Section: Discussionmentioning

confidence: 99%

Prox1 Is a Novel Coregulator of Ff1b and Is Involved in the Embryonic Development of the Zebra Fish Interrenal Primordium

Liu

Gao

Teh

et al. 2003

Molecular and Cellular Biology

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“…The expression of P450scc and other steroidogenic enzymes in the adrenal and gonad requires the action of steroidogenic factor 1 (SF1) an orphan zinc-fi nger transcription factor ( 295,296 ). By contrast, the expression of P450scc in the human placenta is constitutive ( 191 ) and independent of SF1; however, it requires members of the CP2 ( graineyhead ) family of transcription factors (also known as LBP proteins) ( 297-300 ) and TreP-132 ( 301,302 ). Thus, longterm cellular stimulation over the course of days will increase the content of P450scc and the level of basal steroid produced, as well as the capacity of the cell to mount a steroidogenic response.…”

Section: Steroidogenesis and Cytochrome P450mentioning

confidence: 99%

Early steps in steroidogenesis: intracellular cholesterol trafficking

Miller

Bose

2011

Journal of Lipid Research

444

398

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“…Plasmid Gal4-tk80-luc was a luciferase reporter gene under the control of the Gal4-responsive element and plasmid pGal4-Smad1 was a human Smad1 sequence fused with the DNA-binding domain of Gal4 (Pearson et al 1999). P450 scc luciferase reporter constructs containing fragments of the human P450 scc gene spanning from nucleotides -110 to +49, with or without the mutated SF-1-binding site, subcloned in pGL3 vector, were kindly provided by Dr B Staels (Gizard et al 2002). StAR luciferase reporter construct containing fragments of human StAR gene spanning nucleotides -235 to +39 was a gift from Dr J Strauss (Sugawara et al 1996).…”

Section: Reagents and Suppliesmentioning

confidence: 99%

Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells

Aimar¹,

Pisselet²,

Dupont³

et al. 2004

Journal of Molecular Endocrinology

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We have recently reported that bone morphogenetic protein-4 (BMP-4) can inhibit progesterone production by ovine granulosa cells (GCs). Here, we have investigated the underlying mechanisms of this effect in basal as well as in FSH-induced conditions. We have confirmed that treatment with BMP-4 decreased basal GC progesterone secretion and totally abolished FSH-stimulating action. This inhibitory action was associated with a decrease in the expression of cAMP-regulated genes, steroidogenic acute regulatory protein (StAR) and P450 side-chain cleavage (P450 scc) at mRNA and protein levels. However, BMP-4 did not alter basal cAMP production by GCs. In contrast, BMP-4 decreased by half the FSH-induced cAMP production and strongly inhibited cAMP-induced progesterone production. Thus, the inhibitory effect of BMP-4 was exerted both upstream and downstream of cAMP signalling. We next examined the downstream effect, focusing on cAMP-dependent transcription factors, steroidogenic factor-1 (SF-1) and CREB, through the BMP factor signalling intermediary, Smad1. As expected, BMP-4 induced phosphorylation and transcriptional activity of Smad1 in ovine GCs. BMP-4-activated Smad1 did not affect CREB activity but inhibited the transcriptional activity of SF-1 on the canonical SF-1 responsive element. Interestingly, this transcriptional inhibitory mechanism occurred on transfected StAR and P450 scc promoter. Based on these results, we propose that SF-1 is a key target in the inhibitory mechanism exerted by BMP-4 on progesterone synthesis by ovine GCs in culture. Because SF-1 plays an essential role in the differentiation of GCs, our findings could have new implications in understanding the role of BMP family members in the control of ovarian folliculogenesis.

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The Transcriptional Regulating Protein of 132 kDa (TReP-132) Enhances P450scc Gene Transcription through Interaction with Steroidogenic Factor-1 in Human Adrenal Cells

Abstract: The human P450scc gene is regulated by the tissuespecific orphan nuclear receptor, steroidogenic factor-1 (SF-1), which plays a key role in several physiologic processes including steroid synthesis, adrenal and gonadal development, and sexual differentiation.

Cited by 53 publications

References 103 publications

Prox1 Is a Novel Coregulator of Ff1b and Is Involved in the Embryonic Development of the Zebra Fish Interrenal Primordium

Prox1 Is a Novel Coregulator of Ff1b and Is Involved in the Embryonic Development of the Zebra Fish Interrenal Primordium

Early steps in steroidogenesis: intracellular cholesterol trafficking

Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells

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