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Orphan nuclear hormone receptor NR4A1 interacts with HPV16 E2 regulatory protein

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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.

  2. 2.

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

  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.

  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.

  5. 5.

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

  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.

  7. 7.

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

  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.

  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.

  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.

  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.

  12. 12.

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

  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.

  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.

  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.

  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.

  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.

  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.

  19. 19.

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

  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.

  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.

  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.

  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.

  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.

  25. 25.

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

  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.

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Correspondence to Marcin T. Schmidt.

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Key words

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