Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1996 Dec;70(12):8558–8563. doi: 10.1128/jvi.70.12.8558-8563.1996

E5 proteins of human papillomavirus types 11 and 16 transactivate the c-fos promoter through the NF1 binding element.

S L Chen 1, Y K Lin 1, L Y Li 1, Y P Tsao 1, H Y Lo 1, W B Wang 1, T C Tsai 1
PMCID: PMC190948  PMID: 8970980

Abstract

Human papillomavirus type 11 (HPV-11) and HPV-16 contain an E5 gene that can induce c-fos gene expression in mouse fibroblasts. This study investigated the human c-fos promoter characteristics by mapping the c-fos promoter sequence with several deletion and point mutants that confer responsiveness to E5 of HPV-11 or HPV-16. The mutant studies show that NF1 binding sequences within the c-fos promoter were crucial for the induction of the c-fos gene by E5, and the gel shift assay study suggested that E5 of both HPV-11 and HPV-16 is associated, perhaps indirectly, with this NF1 element in the transactivation of the human c-fos promoter. Using an inducible system, we demonstrate that increased induction of the HPV-11 E5 gene in cells led to increased transactivation of the NF1 element. In addition, the transactivating activity of a series of HPV-11 E5 mutants on the NF1 element had a strong correlation with their respective transforming activities.

Full Text

The Full Text of this article is available as a PDF (255.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amemiya K., Traub R., Durham L., Major E. O. Adjacent nuclear factor-1 and activator protein binding sites in the enhancer of the neurotropic JC virus. A common characteristic of many brain-specific genes. J Biol Chem. 1992 Jul 15;267(20):14204–14211. [PubMed] [Google Scholar]
  2. Bouvard V., Matlashewski G., Gu Z. M., Storey A., Banks L. The human papillomavirus type 16 E5 gene cooperates with the E7 gene to stimulate proliferation of primary cells and increases viral gene expression. Virology. 1994 Aug 15;203(1):73–80. doi: 10.1006/viro.1994.1456. [DOI] [PubMed] [Google Scholar]
  3. Chakraborty T., Das G. C. Proteins of the nuclear factor-1 family act as an activator of the late promoter in human polyomavirus BK in vitro. J Gen Virol. 1991 Aug;72(Pt 8):1935–1942. doi: 10.1099/0022-1317-72-8-1935. [DOI] [PubMed] [Google Scholar]
  4. Chen J. Y., Funk W. D., Wright W. E., Shay J. W., Minna J. D. Heterogeneity of transcriptional activity of mutant p53 proteins and p53 DNA target sequences. Oncogene. 1993 Aug;8(8):2159–2166. [PubMed] [Google Scholar]
  5. Chen M., Mermod N., Horwitz M. S. Protein-protein interactions between adenovirus DNA polymerase and nuclear factor I mediate formation of the DNA replication preinitiation complex. J Biol Chem. 1990 Oct 25;265(30):18634–18642. [PubMed] [Google Scholar]
  6. Chen S. L., Han C. P., Tsao Y. P. Construction of site-specific mutants of E5A protein of HPV-11 using the polymerase chain reaction and a single mutant primer. J Virol Methods. 1993 Apr;42(1):89–94. doi: 10.1016/0166-0934(93)90179-u. [DOI] [PubMed] [Google Scholar]
  7. Chen S. L., Huang C. H., Tsai T. C., Lu K. Y., Tsao Y. P. The regulation mechanism of c-jun and junB by human papillomavirus type 16 E5 oncoprotein. Arch Virol. 1996;141(5):791–800. doi: 10.1007/BF01718155. [DOI] [PubMed] [Google Scholar]
  8. Chen S. L., Mounts P. Transforming activity of E5a protein of human papillomavirus type 6 in NIH 3T3 and C127 cells. J Virol. 1990 Jul;64(7):3226–3233. doi: 10.1128/jvi.64.7.3226-3233.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chen S. L., Tsai T. Z., Han C. P., Tsao Y. P. Mutational analysis of human papillomavirus type 11 E5a oncoprotein. J Virol. 1996 Jun;70(6):3502–3508. doi: 10.1128/jvi.70.6.3502-3508.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chen S. L., Tsao Y. P., Lee J. W., Liu H. S., Yang C. M., Tsao L. T. E5a gene of human papillomavirus type 11 is required for initiation but not for maintenance of transformation in NIH 3T3 cells. J Gen Virol. 1994 Aug;75(Pt 8):1953–1960. doi: 10.1099/0022-1317-75-8-1953. [DOI] [PubMed] [Google Scholar]
  11. Chen S. L., Tsao Y. P., Yang C. M., Lin Y. K., Huang C. H., Kuo S. W. Differential induction and regulation of c-jun, junB, junD and c-fos by human papillomavirus type 11 E5a oncoprotein. J Gen Virol. 1995 Nov;76(Pt 11):2653–2659. doi: 10.1099/0022-1317-76-11-2653. [DOI] [PubMed] [Google Scholar]
  12. Chong T., Apt D., Gloss B., Isa M., Bernard H. U. The enhancer of human papillomavirus type 16: binding sites for the ubiquitous transcription factors oct-1, NFA, TEF-2, NF1, and AP-1 participate in epithelial cell-specific transcription. J Virol. 1991 Nov;65(11):5933–5943. doi: 10.1128/jvi.65.11.5933-5943.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chong T., Chan W. K., Bernard H. U. Transcriptional activation of human papillomavirus 16 by nuclear factor I, AP1, steroid receptors and a possibly novel transcription factor, PVF: a model for the composition of genital papillomavirus enhancers. Nucleic Acids Res. 1990 Feb 11;18(3):465–470. doi: 10.1093/nar/18.3.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Conrad M., Bubb V. J., Schlegel R. The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein. J Virol. 1993 Oct;67(10):6170–6178. doi: 10.1128/jvi.67.10.6170-6178.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Conrad M., Goldstein D., Andresson T., Schlegel R. The E5 protein of HPV-6, but not HPV-16, associates efficiently with cellular growth factor receptors. Virology. 1994 May 1;200(2):796–800. doi: 10.1006/viro.1994.1244. [DOI] [PubMed] [Google Scholar]
  16. Dollard S. C., Broker T. R., Chow L. T. Regulation of the human papillomavirus type 11 E6 promoter by viral and host transcription factors in primary human keratinocytes. J Virol. 1993 Mar;67(3):1721–1726. doi: 10.1128/jvi.67.3.1721-1726.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fisch T. M., Prywes R., Roeder R. G. An AP1-binding site in the c-fos gene can mediate induction by epidermal growth factor and 12-O-tetradecanoyl phorbol-13-acetate. Mol Cell Biol. 1989 Mar;9(3):1327–1331. doi: 10.1128/mcb.9.3.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gilman M. Z. The c-fos serum response element responds to protein kinase C-dependent and -independent signals but not to cyclic AMP. Genes Dev. 1988 Apr;2(4):394–402. doi: 10.1101/gad.2.4.394. [DOI] [PubMed] [Google Scholar]
  19. Gounari F., De Francesco R., Schmitt J., van der Vliet P., Cortese R., Stunnenberg H. Amino-terminal domain of NF1 binds to DNA as a dimer and activates adenovirus DNA replication. EMBO J. 1990 Feb;9(2):559–566. doi: 10.1002/j.1460-2075.1990.tb08143.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Grewal T., Theisen M., Borgmeyer U., Grussenmeyer T., Rupp R. A., Stief A., Qian F., Hecht A., Sippel A. E. The -6.1-kilobase chicken lysozyme enhancer is a multifactorial complex containing several cell-type-specific elements. Mol Cell Biol. 1992 May;12(5):2339–2350. doi: 10.1128/mcb.12.5.2339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hennighausen L., Fleckenstein B. Nuclear factor 1 interacts with five DNA elements in the promoter region of the human cytomegalovirus major immediate early gene. EMBO J. 1986 Jun;5(6):1367–1371. doi: 10.1002/j.1460-2075.1986.tb04368.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Howley P. M. Role of the human papillomaviruses in human cancer. Cancer Res. 1991 Sep 15;51(18 Suppl):5019s–5022s. [PubMed] [Google Scholar]
  23. Hwang E. S., Nottoli T., Dimaio D. The HPV16 E5 protein: expression, detection, and stable complex formation with transmembrane proteins in COS cells. Virology. 1995 Aug 1;211(1):227–233. doi: 10.1006/viro.1995.1395. [DOI] [PubMed] [Google Scholar]
  24. Lamb N. J., Fernandez A., Tourkine N., Jeanteur P., Blanchard J. M. Demonstration in living cells of an intragenic negative regulatory element within the rodent c-fos gene. Cell. 1990 May 4;61(3):485–496. doi: 10.1016/0092-8674(90)90530-r. [DOI] [PubMed] [Google Scholar]
  25. Leechanachai P., Banks L., Moreau F., Matlashewski G. The E5 gene from human papillomavirus type 16 is an oncogene which enhances growth factor-mediated signal transduction to the nucleus. Oncogene. 1992 Jan;7(1):19–25. [PubMed] [Google Scholar]
  26. Leptak C., Ramon y Cajal S., Kulke R., Horwitz B. H., Riese D. J., 2nd, Dotto G. P., DiMaio D. Tumorigenic transformation of murine keratinocytes by the E5 genes of bovine papillomavirus type 1 and human papillomavirus type 16. J Virol. 1991 Dec;65(12):7078–7083. doi: 10.1128/jvi.65.12.7078-7083.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Loeken M. R., Brady J. The adenovirus EIIA enhancer. Analysis of regulatory sequences and changes in binding activity of ATF and EIIF following adenovirus infection. J Biol Chem. 1989 Apr 15;264(11):6572–6579. [PubMed] [Google Scholar]
  28. Mermod N., O'Neill E. A., Kelly T. J., Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. doi: 10.1016/0092-8674(89)90108-6. [DOI] [PubMed] [Google Scholar]
  29. Nowock J., Borgmeyer U., Püschel A. W., Rupp R. A., Sippel A. E. The TGGCA protein binds to the MMTV-LTR, the adenovirus origin of replication, and the BK virus enhancer. Nucleic Acids Res. 1985 Mar 25;13(6):2045–2061. doi: 10.1093/nar/13.6.2045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Plumb M., Fulton R., Breimer L., Stewart M., Willison K., Neil J. C. Nuclear factor 1 activates the feline leukemia virus long terminal repeat but is posttranscriptionally down-regulated in leukemia cell lines. J Virol. 1991 Apr;65(4):1991–1999. doi: 10.1128/jvi.65.4.1991-1999.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Runkel L., Shaw P. E., Herrera R. E., Hipskind R. A., Nordheim A. Multiple basal promoter elements determine the level of human c-fos transcription. Mol Cell Biol. 1991 Mar;11(3):1270–1280. doi: 10.1128/mcb.11.3.1270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shaul Y., Ben-Levy R., De-Medina T. High affinity binding site for nuclear factor I next to the hepatitis B virus S gene promoter. EMBO J. 1986 Aug;5(8):1967–1971. doi: 10.1002/j.1460-2075.1986.tb04451.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Straight S. W., Hinkle P. M., Jewers R. J., McCance D. J. The E5 oncoprotein of human papillomavirus type 16 transforms fibroblasts and effects the downregulation of the epidermal growth factor receptor in keratinocytes. J Virol. 1993 Aug;67(8):4521–4532. doi: 10.1128/jvi.67.8.4521-4532.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tsao Y. P., Chu T. Y., Chen T. M., Yang Y. F., Chen S. L. Effects of E5a and E7 genes of human papillomavirus type 11 on immortalized human epidermal keratinocytes and NIH 3T3 cells. Arch Virol. 1994;138(1-2):177–185. doi: 10.1007/BF01310049. [DOI] [PubMed] [Google Scholar]
  35. Tsao Y. P., Li L. Y., Tsai T. C., Chen S. L. Human papillomavirus type 11 and 16 E5 represses p21(WafI/SdiI/CipI) gene expression in fibroblasts and keratinocytes. J Virol. 1996 Nov;70(11):7535–7539. doi: 10.1128/jvi.70.11.7535-7539.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. zur Hausen H. Human papillomaviruses in the pathogenesis of anogenital cancer. Virology. 1991 Sep;184(1):9–13. doi: 10.1016/0042-6822(91)90816-t. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES