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Makorin RING finger protein 1 (MKRN1) has negative and positive effects on RNA polymerase II-dependent transcription

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Abstract

Through its transcriptional activities, the proto-oncoprotein c-jun can regulate cellular proliferation, survival, and differentiation. We have established a novel yeast assay that screens for repressors of c-jun transcriptional activity. This screen led to the identification of a ubiquitously expressed novel RING zinc finger protein, termed Makorin RING zinc finger protein 1 (MKRN1), recently shown to act as an E3 ubiquitin ligase. Overexpression of MKRN1 in mammalian cells inhibited the transcriptional activities of not only c-jun, but also the nuclear receptors, the androgen receptor, and the retinoic acid receptors. Truncation analysis indicates that both the amino and carboxy termini are required for this transrepression activity. Surprisingly, when fused to the heterologous DNA-binding domain of GAL4, MKRN1 activates, rather than inhibits, a GAL4-responsive reporter plasmid. In addition, truncation of either the amino- or carboxy-terminal half of MKRN1 disrupts its transactivation activity, the same observation that was made on its transrepression activity. These results demonstrate that MKRN1 has transcriptional activity and suggest that its transrepression and transactivation functions are mediated by the same mechanism. Interestingly, disruption of MKRN1's ubiquitin ligase activity does not affect its inhibitory transcriptional activity. Thus, MKRN1 may represent a nuclear protein with multiple nuclear functions, including regulating RNA polymerase II-catalyzed transcription.

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References

  1. Karin, M., Liu, Z., and Zandi, E. (1997). Curr. Opin. Cell Biol. 9, 240–246.

    Article  PubMed  CAS  Google Scholar 

  2. Hartl, M., Bader, A. G., and Bister, K. (2003). Curr. Cancer Drug Targets 3, 41–55.

    Article  PubMed  CAS  Google Scholar 

  3. Chinenov, Y. and Kerppola, T. K. (2001). Oncogene 20, 2438–2352.

    Article  PubMed  CAS  Google Scholar 

  4. Dunn, C., Wiltshire, C., MacLaren, A., and Gillespie, D. A. F. (2002). Cell. Signal. 14, 585–593.

    Article  PubMed  CAS  Google Scholar 

  5. Vlaeminck-Guillem, V., Laudet, V., and Duterque-Coquillaud, M. (2003). Med. Sci. 19, 1121–1127.

    Google Scholar 

  6. Miner, J. N., Diamond, M. I., and Yamamoto, K. R. (1991). Cell. Growth Differ. 2, 525–530.

    PubMed  CAS  Google Scholar 

  7. Nakae, K., Nakajima, K., Inazawa, J., Kitaoka, T., and Hirano, T. (1995). J. Biol. Chem. 270, 23795–23800.

    Article  PubMed  CAS  Google Scholar 

  8. Behre, G., Whitmarsh, A. J., Coghlan, M. P., et al. (1999). J. Biol. Chem. 274, 4939–4946.

    Article  PubMed  CAS  Google Scholar 

  9. Wise, S. C., Burmeister, L. A., Zhou, X.-F., et al. (1998). Oncogene 16, 2001–2009.

    Article  PubMed  CAS  Google Scholar 

  10. van Dam, H., Huguier, S., Kooistra, K., et al. (1998). Genes Dev. 12, 1227–1239.

    PubMed  Google Scholar 

  11. Venugopal, R. and Jaiswal, A. K. (1998). Oncogene 17, 3145–3156.

    Article  PubMed  CAS  Google Scholar 

  12. Kerppola, T. K. and Curran, T. (1994). Oncogene 9, 3149–3158.

    PubMed  CAS  Google Scholar 

  13. Pearce, D. and Yamamoto, K. R. (1993). Science 259, 1161–1165.

    Article  PubMed  CAS  Google Scholar 

  14. Peterson, B. R., Sun, L. J., and Verdine, G. L. (1996). Proc. Natl. Acad. Sci. USA 93, 13671–13676.

    Article  PubMed  CAS  Google Scholar 

  15. Bassuk, A. G. and Leiden, J. M. (1995). Immunity 3, 223–237.

    Article  PubMed  CAS  Google Scholar 

  16. Zhang, Y., Feng, X. H., and Derynck, R. (1998). Nature 394, 909–913.

    Article  PubMed  CAS  Google Scholar 

  17. Zhang, X., Wrzeszczynska, M. H., Horvath, C. M., and Darnell, J. E. (1999). Mol. Cell. Biol. 19, 7138–7146.

    PubMed  CAS  Google Scholar 

  18. Li, L., Chambard, J. C., Karin, M., and Olson, E. N. (1992) Genes Dev. 6, 676–689.

    Article  PubMed  CAS  Google Scholar 

  19. Martin, M. L., Lieberman, P. M., and Curran, T. (1996). Mol. Cell. Biol. 16, 2110–2118.

    PubMed  CAS  Google Scholar 

  20. Claret, F. X., Hibi, M., Dhut, S., Toda, T., and Karin, M. (1996). Nature 383, 453–457.

    Article  PubMed  CAS  Google Scholar 

  21. Chen, L. C., Chen, B. K., Chang, J. M., and Chang, W. C. (2004). Biochim. Biophys. Acta 1683, 38–48.

    PubMed  CAS  Google Scholar 

  22. Lee, S. K., Kim, H. J., Na, S. Y., et al. (1998). J. Biol. Chem. 273, 16651–16654.

    Article  PubMed  CAS  Google Scholar 

  23. Piu, F., Aronheim, A., Katz, S., and Karin, M. (2001). Mol. Cell. Biol. 21, 3012–3024.

    Article  PubMed  CAS  Google Scholar 

  24. Ogawa, S., Lozach, J., Jepsen, K., et al. (2004). Proc. Natl. Acad. Sci. USA 101, 14461–14466.

    Article  PubMed  CAS  Google Scholar 

  25. Shemshedini, L., Knauthe, R., Sassone-Corsi, P., Pornon, A., and Gronemeyer, H. (1992). EMBO J. 10, 3839–3849.

    Google Scholar 

  26. Bubulya, A., Wise, S. C., Shen, X.-Q., Burmeister, L. A., and Shemshedini, L. (1996). J. Biol. Chem. 271, 24583–24589.

    Article  PubMed  CAS  Google Scholar 

  27. Tillman, K., Oberfield, J. J., Shen, X.-Q., Bubulya, A., and Shemshedini, L. (1998). Endocrine 9, 193–200.

    Article  PubMed  CAS  Google Scholar 

  28. Gray, T. A., Hernandez, L., Carey, A. H., et al. (2000). Genomics 66, 76–86.

    Article  PubMed  CAS  Google Scholar 

  29. Kim, J. H., Park, S. M., Kang, M. R., et al. (2005). Genes Dev. 19, 776–781.

    Article  PubMed  CAS  Google Scholar 

  30. Howell, B. W., Afar, D. E., Lew, J., et al. (1991)., Mol. Cell. Biol. 11, 568–572.

    PubMed  CAS  Google Scholar 

  31. Zhou, X. F., Shen, X. Q., and Shemshedini, L. (1999). Mol. Endocrinol. 13, 276–285.

    Article  PubMed  CAS  Google Scholar 

  32. Horlein, A. J., Naar, A. M., Heinzel, T., et al. (1995). Nature 377, 397–404.

    Article  PubMed  CAS  Google Scholar 

  33. Chen, J. D. and Evans, R. M. (1995). Nature 377, 454–457.

    Article  PubMed  CAS  Google Scholar 

  34. Matthews, J. M. and Sunde, M. (2002). IUBMB Life 54, 351–355.

    Article  PubMed  CAS  Google Scholar 

  35. Klug, A. and Schwabe, J. W. (1995). FASEB J. 9, 597–604.

    PubMed  CAS  Google Scholar 

  36. Borden, K. L. (2000). J. Mol. Biol. 295, 1103–1012.

    Article  PubMed  CAS  Google Scholar 

  37. Joazeiro, C. A. and Weissman, A. M. (2000). Cell 102, 549–552.

    Article  PubMed  CAS  Google Scholar 

  38. Cairns, C. A. and White, R. J. (1998). EMBO J. 17, 3112–3123.

    Article  PubMed  CAS  Google Scholar 

  39. Xu, L., Glass, C. K., and Rosenfeld, M. G. (1999). Curr. Opin. Genet. Dev. 9, 140–147.

    Article  PubMed  CAS  Google Scholar 

  40. Marmorstein, R., Carey, M., Ptashne, M., and Harrison, S. C. (1992). Nature 356, 408–414.

    Article  PubMed  CAS  Google Scholar 

  41. Marmostein, R. and Harrison, S. C. (1994). Genes Dev. 8, 2504–2512.

    Article  Google Scholar 

  42. Bubulya, A., Chen, S. Y., Fisher, C. J., Zheng, Z., Zhou, X. F., Shen, X. Q., and Shemshedini, L. (2001). J. Biol. Chem. 276, 44704–44711.

    Article  PubMed  CAS  Google Scholar 

  43. Langley, E., Kemppainen, J. A., and Wilson, E. M. (1998). J. Biol. Chem. 273, 92–101.

    Article  PubMed  CAS  Google Scholar 

  44. Chene, P. (2001). Oncogene 20, 2611–2617.

    Article  PubMed  CAS  Google Scholar 

  45. Hirotsune, S., Yoshida, N., Chen, A., et al. (2003). Nature 423, 91–96.

    Article  PubMed  CAS  Google Scholar 

  46. Shenk, J. L., Fisher, C. J., Chen, S. Y., Zhou, X. F., Tillman, K., and Shemshedini, L. (2001). J. Biol. Chem. 276, 38472–38479.

    Article  PubMed  CAS  Google Scholar 

  47. Cheshire, J. L. and Baldwin, A. S. Jr. (1997). Mol. Cell. Biol. 17, 6746–6754.

    PubMed  CAS  Google Scholar 

  48. Shen, X. Q., Bubulya, A., Zhou, X. F., Khazak, V., Golemis, E. A., and Shemshedini, L. (1999). Endocrine 10, 281–289.

    PubMed  CAS  Google Scholar 

  49. Gyuris, J., Golemis, E., Chertkov H., and Brent, R. (1993) Cell 75, 791–803.

    Article  PubMed  CAS  Google Scholar 

  50. Ausubel, F. M., Brent, R., Kingston, R. E., et al., (1998). Current protocols in molecular biology. vol. 2. Wiley, New York.

    Google Scholar 

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Author information

Author notes

  1. Josephat Omwancha

    Present address: Johns Hopkins University, 615 North Wolfe St., Baltimore, MD

  2. Shao-Yong Chen

    Present address: Harvard Medical School, 330 Brookline Avenue, Boston, MA

  3. Christopher J. Fisher & Zhe Zheng

    Present address: Medical University of Ohio, 3000 Arlington Avenne, Toledo, OH

Authors and Affiliations

  1. Department of Biological Sciences, University of Toledo, 43606, Toledo, OH

    Josephat Omwancha, Xiao-Feng Zhou, Shao-Yong Chen, Timour Baslan, Christopher J. Fisher, Zhe Zheng & Lirim Shemshedini

  2. Johns Hopkins University, 615 North Wolfe St., Baltimore, MD

    Changmeng Cai

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  1. Josephat Omwancha
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  2. Xiao-Feng Zhou
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Correspondence to Lirim Shemshedini.

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Omwancha, J., Zhou, XF., Chen, SY. et al. Makorin RING finger protein 1 (MKRN1) has negative and positive effects on RNA polymerase II-dependent transcription. Endocr 29, 363–373 (2006). https://doi.org/10.1385/ENDO:29:2:363

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  • DOI: https://doi.org/10.1385/ENDO:29:2:363

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