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L Martin, Reproduction, perinatal and child health, CHUL Room T1-49, CHUQ Research Centre - Laval University, Quebec City, Quebec, Canada
J Tremblay, Reproduction, perinatal and child health, CHUL Room T1-49, CHUQ Research Centre - Laval University, Quebec City, Quebec, G1V 4G2, Canada
Correspondence: Jacques J Tremblay, Email: Jacques-J.Tremblay{at}crchul.ulaval.ca
Abstract
The steroidogenic acute regulatory protein (STAR) plays an essential role in steroid biosynthesis in steroidogenic cells. It is involved in the transport of cholesterol through the mitochondrial membrane where the first step of steroidogenesis occurs. Star gene expression in testicular Leydig cells is regulated by the pituitary luteinizing hormone through the cAMP signaling pathway. So far, several transcription factors have been implicated in the regulation of Star promoter activity in these cells. These include the nuclear receptors NUR77 and SF1, AP-1 family members (particularly c-JUN), GATA4, C/EBPβ, DLX5/6, and CREB. Some of these factors were also shown to act in a cooperative manner to further enhance Star promoter activity. Here we report that NUR77 and c-JUN have additive effects on the Star promoter. These effects were abolished only when both elements, NUR77 at -95 bp and AP-1 at -78 bp, were mutated. Consistent with this, in vitro co-immunoprecipitation revealed that NUR77 and c-JUN interact and that this interaction is mediated through part of the ligand binding domain of NUR77. Furthermore, we found that SF1 could cooperate with c-JUN on the mouse Star promoter but this cooperation involved different regulatory elements. Collectively, our data not only provide new insights into the molecular mechanisms that control mouse Star transcription in Leydig cells but also reveal a novel mechanism for the regulation of NUR77 dependent genes in tissues where NUR77 and c-JUN factors are co-expressed.
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H. A. LaVoie and S. R. King Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B Experimental Biology and Medicine, August 1, 2009; 234(8): 880 - 907. [Abstract] [Full Text] [PDF] |
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