Protein kinase A-dependent cooperation between GATA and CCAAT/enhancer-binding protein transcription factors regulates steroidogenic acute regulatory protein promoter activity.
Steroidogenic acute regulatory protein (StAR) is an essential cholesterol transporter in steroidogenic tissues. Hormone-induced StAR expression is regulated through the cAMP-dependent pathway involving activation of protein kinase A (PKA). The StAR promoter contains several conserved DNA regulatory elements. These include binding sites for steroidogenic factor 1, CCAAT/enhancer-binding protein (C/EBP), and GATA transcription factors. Although these elements are important for StAR promoter activity, how the various transcription factors that bind these elements cooperate to confer cAMP responsiveness remains poorly understood. As induction of StAR transcription by cAMP in steroidogenic MA-10 cells does not require de novo protein synthesis, this suggests that all essential transcription factors are present and that posttranslational modifications of the factors are involved. We now report that GATA-4 is phosphorylated in MA-10 cells in response to cAMP and in heterologous CV-1 cells, GATA-4 transcriptional activity is stimulated by PKA. Moreover, we show that GATA-4 and C/EBPbeta directly interact in vitro and in vivo and synergistically activate the StAR promoter in CV-1 cells exclusively in the presence of PKA. As PKA-dependent synergy was also observed with other GATA and C/EBP family members, this transcriptional cooperation may contribute to hormone-stimulated StAR expression in all steroidogenic tissues.
Tremblay
Jacques J
JJ
Ontogeny and Reproduction Research Unit, Centre Hospitalier de l'Université Laval (CHUL) Research Center, Ste-Foy, Québec, Canada G1V 4G2.
Hamel
Frédéric
F
Viger
Robert S
RS
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D050991:GATA4 Transcription Factor; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000502:physiology*; D000098682:Steroidogenic Acute Regulatory Protein
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D010750:Phosphoproteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000098682:Steroidogenic Acute Regulatory Protein; C515058:steroidogenic factor 1, mouse; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases