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Effects of mutating different steroidogenic factor-1 protein regions on gene regulation

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Abstract

The involvement of cyclic adenosine monophosphate cAMP-dependent protein kinase A (PKA) in the regulation of the steroidogenic acute regulatory protein (StAR) and the high-density lipoprotein receptor (HDL-R) genes by steroidogenic factor-1 (SF-1) and cAMP were examined. Cotransfection studies carried out in Kin 8 cells, a Y1 cell line (mouse adrenal) with a mutation in the type I PKA regulatory subunit, demonstrated that an intact PKA is required for maximal activation and that SF-1 participates in cAMP regulation of these genes. Site-directed mutational analysis was performed to examine which SF-1 regions could be involved in SF-1 transcriptional activation of the StAR and HDL-R genes. SF-1 regions protein analyzed were amino acids Thr 60, Ser 203, Ser 431, Thr 462, and the activation function-2 domain (amino acids 449–462). Plasmids encoding each of the mutated SF-1 proteins were cotransfected with the StAR and HDL-R promoter constructs into human bladder carcinoma (HTB-9) cells in the presence or absence of dibutyryl cAMP. The results of these studies suggest that although SF-1 is required for optimal promoter response to cAMP, transcriptional activation of genes by SF-1 and cAMP are promoter dependent, perhaps resulting from gene-specific interactions of this transcription factor with other regulatory proteins.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of South Florida, 4 Columbia Drive, Room 529, 33606, Tampa, FL

    Dayami Lopez, Anna C. Nackley, Wendy Shea-Eaton &  Mark P. McLean

  2. Department of Biochemistry and Molecular Biology, University of South Florida, Tampa, FL

    Dayami Lopez, Anna C. Nackley, Wendy Shea-Eaton &  Mark P. McLean

  3. The Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada

    Jiaping Xue & Bernard P. Schimmer

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  1. Dayami Lopez
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  2. Anna C. Nackley
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  3. Wendy Shea-Eaton
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  6. Mark P. McLean
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Correspondence to Mark P. McLean.

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Lopez, D., Nackley, A.C., Shea-Eaton, W. et al. Effects of mutating different steroidogenic factor-1 protein regions on gene regulation. Endocr 14, 353–362 (2001). https://doi.org/10.1385/ENDO:14:3:353

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  • DOI: https://doi.org/10.1385/ENDO:14:3:353

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