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c-Fos dimerization with c-Jun represses c-Jun enhancement of androgen receptor transactivation

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Abstract

The transcriptional activity of the human androgen receptor (hAR), like other nuclear receptors, is dependent on accessory factors. One such factor is c-Jun, which has been shown to have a selective function of mediating androgen receptor-dependent transactivation. This c-Jun activity is inhibited by c-Fos, another protooncoprotein that can dimerize with c-Jun to form the transcription factor AP-1. Here we show that c-Jun mediates hAR-induced transactivation from the promoter of the androgen-regulated gene, human kallikrein-2 (hKLK2), and c-Fos blocks this activity. Using c-Fos truncation mutants and measuring hKLK2-dependent transcription, we have determined that the bZIP region of c-Fos is required and sufficient for inhibiting c-Jun enhancement of hAR transactivation. Further truncation analysis of the bZIP shows that the c-Fos dimerization function, mediated through the leucine zipper, is essential for the negative activity, whereas DNA binding, mediated through the basic region, is dispensable. These results suggest that heterodimerization by c-Fos with c-Jun blocks c-Jun’s ability to enhance hAR-induced transactivation.

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Author information

Author notes

  1. Karl Tillman

    Present address: Department of Research, Beth Israel Deaconess Medical Center, Boston, MA

  2. Jennifer L. Oberfield

    Present address: Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, NC

Authors and Affiliations

  1. Department of Biology, University of Toledo, 2801 West Bancroft, 43606-3390, Toledo, OH

    Karl Tillman, Jennifer L. Oberfield, Xi-Qiang Shen, Athanasios Bubulya &  Lirim Shemshedini

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  1. Karl Tillman
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  2. Jennifer L. Oberfield
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  3. Xi-Qiang Shen
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  4. Athanasios Bubulya
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  5. Lirim Shemshedini
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Correspondence to Lirim Shemshedini.

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Tillman, K., Oberfield, J.L., Shen, XQ. et al. c-Fos dimerization with c-Jun represses c-Jun enhancement of androgen receptor transactivation. Endocr 9, 193–200 (1998). https://doi.org/10.1385/ENDO:9:2:193

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  • DOI: https://doi.org/10.1385/ENDO:9:2:193

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