Abstract
The human androgen receptor (hAR) is a member of the nuclear receptor superfamily and functions as a ligand-inducible transcription factor. We have previously proposed that c-Jun mediates the transcriptional activity of this receptor. The modular nature of hAR was used in this study to generate several fusions with the heterologous DNA-binding domain of the yeast transcription factor GAL4 in an attempt to identify the c-Jun-responsive domains within the receptor. Our results suggest that the target of c-Jun action is the amino terminus (AB region) of the receptor and that hAR amino acids 502–521 are critical for the c-Jun response. Additionally, amino acids 503–555 were shown to harbor an autonomous transactivation that is stimulated by c-Jun. Furthermore, we demonstrated that transcription intermediary factor-2 (TIF-2), a coactivator that acts on the activation function-2, stimulates the full-length hAR. These results suggest that c-Jun and TIF-2 can work together as coactivators on the hAR by targeting distinct portions of the receptor.
Similar content being viewed by others
References
Evans, R. M. (1988). Science 240, 889–895.
Beato, M. (1989). Cell 56, 335–344.
Gronemeyer, H. (1992). FASEB J. 6, 2524–2529.
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schutz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., and Evans, R. M. (1995). Cell 83, 835–839.
Durand, B., Saunders, M., Gaudon, C., Roy, B., Losson, R., and Chambon, P. (1994). EMBO J. 13, 5370–5382.
Simental, J. A., Sar, M., Lane, M. V., French, F. S., and Wilson, E. M. (1991). J. Biol. Chem. 266, 510–518.
Jenster, G., van der Korput, H. A., van Vroohoven, C., van der Kwast, T. H., Trapman, J., and Brinkmann, A. O. (1991). Mol. Endocrinol. 10, 1396–1404.
Jenster, G., van der Korput, H. A. G. M., Trapman, J., Brinkmann, A. O. (1995). J. Biol. Chem. 270, 7341–7346.
Chamberlain, N. L., Whitacre, D. C., and Miesfeld, R. L. (1996). J. Biol. Chem. 271, 26,772–26,778.
McEwan, I. J. and Gustafsson, J.-A., (1997). Proc. Natl. Acad. Sci. USA 94, 8485–8490.
Snoek, R., Rennie, P. S., Kasper, S., Matusik, R. J., and Bruchovsky, N. (1996). J. Steroid Biochem. Mol. Biol. 59, 243–250.
Moilanen, A., Rouleau, N., Ikonen, T., Palvimo, J. J., and Janne, O. A. (1997). FEBS Lett. 412, 355–358.
Berrevoets, C. A., Doesburg, P., Steketee, K., Trapman, J., and Brinkmann, A. O. (1998). Mol. Endocrinol. 12, 1172–1183.
Alen, P., Claessens, F., Verhoeven, G., Rombauts, W., and Peeters, B. (1999). Mol. Cell. Biol. 19, 6085–6097.
Aarnisalo, P., Palvimo, J. J., and Janne, O. A., (1998). Proc. Natl. Acad. Sci. USA 95, 2122–2127.
Verrijzer, C. P. and Tjian, R. (1996). Trends Biochem. Sci. 21, 338–342.
Voegel, J. J., Heine, M. J. S., Zechel, C., Chambon, P., and Gronemeyer, H. (1996). EMBO J. 15, 3667–3675.
Yeh, S. and Chang, C. (1996). Proc. Natl. Acad. Sci. USA 93, 5517–5521.
Hsiao, P. W. and Chang, C. (1999). J. Biol. Chem. 274, 22,373–22,379.
Angel, P. and Karin, M. (1991). Biochimica Biophysica Acta 1072, 129–157.
Shemshedini, L., Knauthe, R., Sassone-Corsi, P., Pornon, A., and Gronemeyer, H. (1991). EMBO J. 10, 3839–3849.
Tillman, K., Oberfield, J. L., Shen, X.-Q., Bubulya, A., and Shemshedini, L., (1998). Endocrine 9, 193–200.
Bubulya, A., Wise, S. C., Shen, X. Q., Burmeister, L. A., and Shemshedini, L. (1996). J. Biol. Chem. 271, 24,583–24,589.
Wise, S. C., Burmeister, L. A., Zhou, X.-F., Bubulya, A., Oberfield, J. L., Birrer, M. J., and Shemshedini, L. (1998). Oncogene 16, 2001–2009.
Pandjaitan, B., Eibensteiner, P. B., Vrtala, S., Hayek, B., Grote, M., Reichelt, R., Rumpold, H., Valenta, R., and Spitzauer, S. (1999). Gene 237, 333–342.
Onate, S. A., Boonyaratanakornkit, V., Spencer, T. E., Tsai, S. Y., Tsai, M. J., Edwards, D. P., and O’Malley, B. W. (1998). J. Biol. Chem. 273, 12,101–12,108.
Anzik, S. L., Kononen, J., Walker, R. L., Azorsa, D. O., Tanner, M. M., Guan, X.-Y., Sauter, G., Kallionemi, O.-P., Trent, J. M., and Meltzer, P. S. (1997). Science 277, 965–968.
Baniahmad, C., Nawaz, Z., Baniahmad, A., Gleeson, M. A., Tsai, M. J., and O’Malley, B. W. (1995). Mol. Endocrinol. 9, 34–44.
Chiba, H., Muramatsu, M., Nomoto, A., and Kato, H. (1994). Nucleic Acids Res. 22, 1815–1820.
Hong, H., Kohli, K., Trivedi, A., Johnson, D. L., and Stallcup, M. R. (1996). Proc. Natl. Acad. Sci. USA 93, 4948–4952.
Jacq, X., Brou, C., Lutz, Y., Davidson, I., Chambon, P. and Tora, L. (1994). Cell 79, 107–117.
Kamei, Y., Xu, L., Heinzel, T., Torchia, J., Kurokawa, R., Gloss, B., Lin, S. C., Heyman, R. A., Rose, D. W., Glass, C. K., and Rosenfeld, M. G. (1996). Cell 85, 403–414.
Le Douarin, B., Zechel, C., Garnier, J.-M., Lutz, Y., Tora, L., Pierrat, B., Heery, D., Gronemeyer, H., Chambon, P., and Losson, R. (1995). EMBO J. 14, 2020–2033.
Glass, C. K., Rose, D. W., and Rosenfeld, M. G., (1997). Curr. Opin. Cell Biol. 9, 222–232.
McPhaul, M. J. (1999). J. Steroid Biochem. Mol. Biol. 69, 315–322.
Ikonen, T., Palvimo, J. J., and Janne, O. A. (1997). J. Biol. Chem. 272, 29,821–29,828.
Bannister, A. J., Oehler, T., Wilhelm, D., Angel, P., and Kouzarides, T. (1995). Oncogene 11, 2509–2514.
Smith, C. L., Onate, S. A., Tsai, M. J., and O’Malley, B. W. (1996). Proc. Natl. Acad. Sci. USA 93, 8884–8888.
Gronemeyer, H., Turcotte, B., Quirin-Stricker, C., Bocquel, M. T., Meyer, M. E., Krozowski, Z., Jelsch, J. M., Lerouge, T., Garnier, J. M., and Chambon, P. (1987). EMBO J. 6, 3985–3994.
Gyuris, J., Golemis, E. A., Chertkov, H., and Brent, R. (1993). Cell 75, 791–803.
Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A., and Struhl, K. (1995). Current protocols in molecular biology, vol. 2. Wiley & Sons: New York.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bubulya, A., Zhou, XF., Shen, XQ. et al. c-Jun targets amino terminus of androgen receptor in regulating androgen-responsive transcription. Endocr 13, 55–62 (2000). https://doi.org/10.1385/ENDO:13:1:55
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/ENDO:13:1:55