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Orphan nuclear hormone receptor NR4A1 interacts with HPV16 E2 regulatory protein

Cellular & Molecular Biology Letters volume 11, pages102–108(2006)Cite this article

Abstract

The human NR4A1 orphan receptor is a member of the TR3 steroid receptor superfamily, which binds DNA at the NBRE and NurRE responsive elements. The TR3 receptors are involved in the regulation of differentiation, proliferation and apoptosis. We report that NR4A1 interacts with human papillomavirus type 16 (HPV16) E2 protein — a key papillomavirus regulatory factor. This interaction might be involved in the transcription regulation of the HPV16 genes and the regulation of infected cell homeostasis.

Abbreviations

HPV:

human papillomavirus

EGFP:

enhanced green fluorescent protein

HA:

hemagglutinin

References

  1. 1.

    Aranda, A. and Pascual, A. Nuclear hormone receptors and gene expression. Physiol. Rev. 81 (2001) 1269–1304.

    PubMed  CAS  Google Scholar 

  2. 2.

    Giguere, V. Orphan nuclear receptors: From gene to function. Endocr. Rev. 20 (1999) 689–725.

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    Hsu, H.C., Zhou, T. and Mountz, J.D. Nur77 family of nuclear hormone receptors. Curr. Drug Targets Inflamm. Allergy 3 (2004) 413–423.

    PubMed  CAS  Article  Google Scholar 

  4. 4.

    Lin, B., Kolluri, S.K., Lin, F., Liu, W., Han, Y.H., Cao, X., Dawson, M.I., Reed, J.C. and Zhang, X.K. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 116 (2004) 527–540.

    PubMed  CAS  Article  Google Scholar 

  5. 5.

    Winoto, A. and Littman, D.R. Nuclear hormone receptors in T lymphocytes. Cell 109 (2002) S57–S66.

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    zur Hausen, H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J. Natl. Cancer. Inst. 92 (2000) 690–698.

    PubMed  Article  Google Scholar 

  7. 7.

    zur Hausen, H. Papillomavirus infections — a major cause of human cancers. Biochim. Biophys. Acta 1288 (1996) F55–F78.

    PubMed  Google Scholar 

  8. 8.

    Nishimura, A., Ono, T., Ishimoto, A., Dowhanick, J.J., Frizzell, M.A., Howley, P.M. and Sakai, H. Mechanisms of human papillomavirus E2-mediated repression of viral oncogene expression and cervical cancer cell growth inhibition. J. Virol. 74 (2000) 3752–3760.

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    Bouvard, V., Storey, A., Pim, D. and Banks, L. Characterization of the human papillomavirus E2 protein: evidence of trans-activation and trans-repression in cervical keratinocytes. EMBO J. 13 (1994) 5451–5459.

    PubMed  CAS  Google Scholar 

  10. 10.

    Hou, S.Y., Wu, S.Y. and Chiang, C.M. Transcriptional activity among high and low risk human papillomavirus E2 proteins correlates with E2 DNA binding. J. Biol. Chem. 277 (2002) 45619–45629.

    PubMed  CAS  Article  Google Scholar 

  11. 11.

    O’Connor, M., Chan, S.Y. and Bernard, H.U. Transcription factor binding sites in the long control region of genital HPVs, in: Human Papillomaviruses 1995 compendium vol. III. (Myers, G., Bernard, H.U. and Deliuset, H. Eds), Los Alamos USA, Los Alamos National Laboratory Press, 1995, 21–40.

    Google Scholar 

  12. 12.

    Fields, S. and Song, O.-K. A novel genetic system to detect protein protein interactions. Nature 340 (1989) 245–246.

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    Vidal, M. The reverse two-hybrid system, in: The Two-Hybrid System (Bartel, P. and Fields, S., Eds.), Oxford University Press, New York, 1997, 109–147.

    Google Scholar 

  14. 14.

    Vidal, M., Brachmann, R.K., Fattaey, A., Harlow, E. and Boeke, J.D. Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions. Proc. Natl. Acad. Sci. USA 93 (1996) 10315–10320.

    PubMed  CAS  Article  Google Scholar 

  15. 15.

    Tootle, T.L. and Rebay, I. Post-translational modifications influence transcription factor activity: a view from the ETS superfamily. Bioessays 27 (2005) 285–298.

    PubMed  CAS  Article  Google Scholar 

  16. 16.

    Calkhoven, C.F. and Ab, G. Multiple steps in the regulation of transcription-factor level and activity. Biochem. J. 317 (1996) 329–342.

    PubMed  CAS  Google Scholar 

  17. 17.

    Sanders, C.M., Stern, P.L. and Maitland, N.J. Characterization of human papillomavirus type 16 E2 protein and subdomains expressed in insect cells. Virology 211 (1995) 418–433.

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    Li, Y. and Lau, L.F. Adrenocorticotropic hormone regulates the activities of the orphan nuclear receptor Nur77 through modulation of phosphorylation. Endocrinol. 138 (1997) 4138–4146.

    CAS  Article  Google Scholar 

  19. 19.

    Whitmarsh, A.J. and Davis, R.J. Regulation of transcription factor function by phosphorylation. Cell Mol. Life Sci. 57 (2000) 1172–1183.

    PubMed  CAS  Article  Google Scholar 

  20. 20.

    Lee, H.J. and Chang, C. Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter. J. Biol. Chem. 270 (1995) 5434–5440.

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    Lee, H.J., Kokontis, J., Wang, K.C. and Chang, C. The use of a DNA-binding domain replacement method for the detection of a potential TR3 orphan receptor response element in the mouse mammary tumor virus long terminal repeat. Biochem. Biophys. Res. Commun. 194 (1993) 97–103.

    PubMed  CAS  Article  Google Scholar 

  22. 22.

    Liu, X., Chen, X., Zachar, V., Chang, C. and Ebbesen, P. Transcriptional activation of human TR3/nur77 gene expression by human T-lymphotropic virus type I Tax protein through two AP-1-like elements. J. Gen. Virol. 80 (1999) 3073–3081.

    PubMed  CAS  Google Scholar 

  23. 23.

    Rohr, O., Schwartz, C., Hery, C., Aunis, D., Tardieu, M. and Schaeffer, E. The nuclear receptor chicken ovalbumin upstream promoter transcription factor interacts with HIV-1 Tat and stimulates viral replication in human microglial cells. J. Biol. Chem. 275 (2000) 2654–2660.

    PubMed  CAS  Article  Google Scholar 

  24. 24.

    Collins, L.L., Lin, D.L., Mu, X.M. and Chang, C. Feedback regulation between orphan nuclear receptor TR2 and human papilloma virus type 16. J. Biol. Chem. 276 (2001) 27316–27321.

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    Bernard, H.U. Gene expression of genital human papillomaviruses and considerations on potential antiviral approaches. Antivir. Theor. 7 (2002) 219–237.

    CAS  Google Scholar 

  26. 26.

    Lee, J.M., Lee, K.H., Weidner, M., Osborne, B.A. and Hayward, S.D. Epstein-Barr virus EBNA2 blocks Nur77-mediated apoptosis. Proc. Natl. Acad. Sci. USA 99 (2002) 11878–11883.

    PubMed  CAS  Article  Google Scholar 

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Affiliations

  1. Department of Biotechnology and Food Microbiology, August Cieszkowski University of Agriculture, Wojska Polskiego 48, 60-627, Poznań, Poland

    Agnieszka K. Olejnik-Schmidt & Marcin T. Schmidt

  2. Department of Molecular Virology, Adam Mickiewicz University, Międzychodzka 5, 60-371, Poznań, Poland

    Agnieszka K. Olejnik-Schmidt & Anna Goździcka-Józefiak

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  1. Agnieszka K. Olejnik-Schmidt
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  2. Marcin T. Schmidt
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  3. Anna Goździcka-Józefiak
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Correspondence to Marcin T. Schmidt.

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Olejnik-Schmidt, A.K., Schmidt, M.T. & Goździcka-Józefiak, A. Orphan nuclear hormone receptor NR4A1 interacts with HPV16 E2 regulatory protein. Cell. Mol. Biol. Lett. 11, 102–108 (2006). https://doi.org/10.2478/s11658-006-0010-x

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Key words

  • NR4A1
  • Nur77
  • E2
  • HPV16
  • Two-hybrid system
  • Nuclear localization
  • Colocalization studies

Cellular & Molecular Biology Letters

ISSN: 1689-1392

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