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Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins

Abstract

We have examined the possibility that the E7 proteins of the high-risk human papillomavirus (HPV) type 16 and 18 and the oncogenic adenovirus (Ad) type 12 E1A protein share the ability to down-regulate the expression of components of the antigen processing and presentation pathway, as a common strategy in the evasion of immune surveillance during the induction of cell transformation. Expression of the HPV 18 E7 oncoprotein, like Ad 12 E1A, resulted in repression of the major histocompatibility complex (MHC) class I heavy chain promoter, as well as repression of a bidirectional promoter that regulates expression of the genes encoding the transporter associated with antigen processing subunit 1 (TAP1) and a proteasome subunit, low molecular weight protein 2 (LMP2). HPV 16 E7 also caused a reduction in class I heavy chain promoter activity, however it did not have any significant effect on the activity of the bidirectional promoter. Interestingly, expression of the low-risk HPV 6b E7 protein resulted in an increase in MHC class I heavy chain promoter activity, while repressing the TAP1/LMP2 promoter. Interference with the class I pathway could also explain the ability of low-risk HPVs in inducing benign lesions.

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References

  • Ackrill AM and Blair GE. . 1988 Oncogene 3: 483–487.

  • Arends MJ, Donaldson YK, Duvall E, Wyllie AH and Bird CC. . 1993 Human Pathol. 24: 432–437.

  • Baas EJ, van Santen H-M, Kleijmeer MJ, Geuze HJ, Peters PJ and Ploegh HL. . 1992 J. Exp. Med. 176: 147–156.

  • Barbosa MS, Vass WC, Lowy DR and Schiller JT. . 1991 J. Virol. 65: 292–298.

  • Bartholomew J, Tinsley JM and Stern PL. . 1995 Modulation of MHC Antigen Expression and Disease: MHC Expression in HPV-associated cervical cancer. Blair GE, Pringle CR, Maudesley DJ (eds). Cambridge University Press: Cambridge pp. 233–250.

  • Blair GE and Hall KT. . 1998 Semin. Virol. 8: 387–397.

  • Burger RA, Monk BJ, Kurosaki T, Antonculver H, Vesilev SA, Berman ML and Wilczynski SP. . 1996 J. Natl. Cancer Inst. 88: 1361–1368.

  • Byrd PJ, Chia W, Rigby PWJ and Gallimore PH. . 1982 J. Gen. Virol. 60: 279–293.

  • Cerundolo V, Kelly A, Elliott T, Trowsdale J and Townsend A. . 1995 Eur. J. Immunol. 25: 554–562.

  • Connor ME and Stern PL. . 1990 Int. J. Cancer 46: 1029–1034.

  • Cox JT. . 1995 Bailliere's Clin. Obstet. Gynecol. 9: 1–37.

  • Cromme FV, Meijer CJLM, Snijders PJF, Uyterlinde A, Kenemans P, Helmerhorst T, Stern PL, van den Brule AJC and Walboomers JMM. . 1993a Br. J. Cancer 67: 1372–1380.

  • Cromme FV, Snijders PJF, van den Brule AJC, Kenemans P, Meijer CJLM and Walboomers JMM. . 1993b Oncogene 8: 2969–2975.

  • Cromme FV, Airey J, Heemels M-T, Ploegh HL, Keating PJ, Stern PL, Meijer CJLM and Walboomers JMM. . 1994a J. Exp. Med. 179: 335–340.

  • Cromme FV, van Bommel P, Walboomers JMM, Gallee MPW, Stern PL, Kenemans P, Helmerhorst T and Meijer CJLM. . 1994b Br. J. Cancer 69: 1176–1181.

  • Dery CV, Herrmann CH and Mathews MB. . 1987 Oncogene 2: 15–23.

  • Dyson N, Howley PM, Münger K and Harlow E. . 1989 Science 243: 934–937.

  • Elliott T. . 1997 Adv. Immunol. 65: 47–109.

  • Gorman C. . 1985 DNA Cloning, Vol. II: A Practical Approach I. Glover DM (ed). IRL Press: Oxford pp. 143–190.

  • Heemels M-T and Ploegh H. . 1995 Annu. Rev. Biochem. 64: 463–491.

  • Herrmann CH, Dery CV and Mathews MB. . 1987 Oncogene 2: 25–35.

  • Keating PJ, Cromme FV, Duggan-Keen M, Snijders PJF, Walboomers JMM, Hunter RD, Dyer PA and Stern PL. . 1995 Br. J. Cancer 72: 405–411.

  • Kimura G, Itagaki S. and Summers J. . 1975 Int. J. Cancer 15: 694–706.

  • Matlashewski G, Schneider J, Banks L, Jones N, Murray A and Crawford L. . 1987 EMBO J. 6: 1741–1746.

  • Nishitani J, Nishinaka T, Cheng C-H, Rong W, Yokoyama KK and Chiu R. . 1999 J. Biol. Chem. 274: 5454–5461.

  • Phelps WC, Yee CL, Münger K and Howley PM. . 1988 Cell 53: 539–547.

  • Phelps WC, Bagchi S, Barnes JA, Raychaudhuri P, Kraus V, Münger K, Howley PM and Nevins JR. . 1991 J. Virol. 65: 6922–6930.

  • Proffitt JL, Sharma E and Blair GE. . 1994 Nucleic Acids Res. 22: 4779–4788.

  • Proffitt JA and Blair GE. . 1997 FEBS Lett. 400: 141–144.

  • Rey O, Lee S and Park NH. . 2000 J. Virol. 74: 4912–4918.

  • Schneider-Gaedicke A and Schwartz E. . 1986 EMBO J. 5: 2285–2292.

  • Smotkin D and Wettstein FO. . 1986 Proc. Natl. Acad. Sci. USA 83: 4680–4684.

  • Stern PL. . 1996 Adv. Cancer Res. 69: 175–211.

  • Storey A, Pim D, Murray A, Ostborn K, Banks L and Crawford L. . 1988 EMBO J. 6: 1815–1820.

  • Townsend A, Elliott T, Cerundolo V, Foster L, Barber B and Tse A. . 1990 Cell 62: 285–295.

  • van Endert PM. . 1999 Curr. Opin. Immunol. 11: 82–88.

  • Wilczynski SP, Pearlman L and Walker J. . 1988 Virology 166: 624–627.

  • Wilczynski SP, Oft M, Cook N, Liao SY and Iftner T. . 1993 Hum. Pathol. 24: 96–102.

  • Williams DB, Vassilakos A and Suh W-K. . 1996 Trends Cell Biol. 6: 267–273.

  • Zwerschke W and Jansen-Dürr P. . 2000 Adv. Cancer Res. 78: 1–29.

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Acknowledgements

We would like to thank JT Schiller (National Cancer Institute, USA) for kindly providing the HPV 6b, 16 and 18 E7 expression vectors. The pE2ACAT construct was a kind gift from MB Mathews (University of Medicine and Dentistry, New Jersey at Newark, USA). We would also like to thank Lindsay J Stanbridge and Luke Stockwin for helpful discussions. This work was supported by Yorkshire Cancer Research.

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Georgopoulos, N., Proffitt, J. & Blair, G. Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins. Oncogene 19, 4930–4935 (2000). https://doi.org/10.1038/sj.onc.1203860

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Keywords

  • human papillomavirus
  • E7
  • MHC class I
  • TAP1
  • LMP2
  • transcriptional repression

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