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. 1996 Jul;70(7):4839–4844. doi: 10.1128/jvi.70.7.4839-4844.1996

C/EBPbeta is a negative regulator of human papillomavirus type 11 in keratinocytes.

H Wang 1, K Liu 1, F Yuan 1, L Berdichevsky 1, L B Taichman 1, K Auborn 1
PMCID: PMC190429  PMID: 8676519

Abstract

We have evaluated the impact of the CCAAT enhancer-binding protein (C/EBP) transcription factors on human papillomavirus type 11 (HPV11). C/EBPbeta is in nuclei of cultured foreskin keratinocytes and binds its consensus sequence in HPV11 DNA. We have used the novel approach of depleting the availability of C/EBPs in vivo using nuclease-resistant oligomers containing C/EBP DNA binding sites. In cultured foreskin keratinocytes containing replicating HPV11 DNA, levels of both HPV11 transcripts and HPV DNA increase after treatment with oligomers; containing the C/EBPbeta DNA binding motif. These results indicate that C/EBPbeta is a repressor for HPV11 in keratinocytes.

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Selected References

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  1. Akira S., Isshiki H., Nakajima T., Kinoshita S., Nishio Y., Natsuka S., Kishimoto T. Regulation of expression of the interleukin 6 gene: structure and function of the transcription factor NF-IL6. Ciba Found Symp. 1992;167:47–67. doi: 10.1002/9780470514269.ch4. [DOI] [PubMed] [Google Scholar]
  2. Akira S., Kishimoto T. IL-6 and NF-IL6 in acute-phase response and viral infection. Immunol Rev. 1992 Jun;127:25–50. doi: 10.1111/j.1600-065x.1992.tb01407.x. [DOI] [PubMed] [Google Scholar]
  3. Alam T., An M. R., Papaconstantinou J. Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response. J Biol Chem. 1992 Mar 15;267(8):5021–5024. [PubMed] [Google Scholar]
  4. Albers K. M., Setzer R. W., Taichman L. B. Heterogeneity in the replicating population of cultured human epidermal keratinocytes. Differentiation. 1986;31(2):134–140. doi: 10.1111/j.1432-0436.1986.tb00394.x. [DOI] [PubMed] [Google Scholar]
  5. Amati B., Land H. Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death. Curr Opin Genet Dev. 1994 Feb;4(1):102–108. doi: 10.1016/0959-437x(94)90098-1. [DOI] [PubMed] [Google Scholar]
  6. Angrand P. O., Rousset J. P., Weiss M. C. Cell phenotype, binding affinity and promoter structure modulate transactivation by HNF1 and LAP. J Cell Sci. 1992 Dec;103(Pt 4):1083–1092. doi: 10.1242/jcs.103.4.1083. [DOI] [PubMed] [Google Scholar]
  7. Auborn K. J., Galli R. L., Dilorenzo T. P., Steinberg B. M. Identification of DNA-protein interactions and enhancer activity at the 5' end of the upstream regulatory region in human papillomavirus type 11. Virology. 1989 May;170(1):123–130. doi: 10.1016/0042-6822(89)90359-0. [DOI] [PubMed] [Google Scholar]
  8. Auborn K. J., Steinberg B. M. A key DNA-protein interaction determines the function of the 5'URR enhancer in human papillomavirus type 11. Virology. 1991 Mar;181(1):132–138. doi: 10.1016/0042-6822(91)90477-s. [DOI] [PubMed] [Google Scholar]
  9. Bedell M. A., Hudson J. B., Golub T. R., Turyk M. E., Hosken M., Wilbanks G. D., Laimins L. A. Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation. J Virol. 1991 May;65(5):2254–2260. doi: 10.1128/jvi.65.5.2254-2260.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cao Z., Umek R. M., McKnight S. L. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 Sep;5(9):1538–1552. doi: 10.1101/gad.5.9.1538. [DOI] [PubMed] [Google Scholar]
  11. Clusel C., Ugarte E., Enjolras N., Vasseur M., Blumenfeld M. Ex vivo regulation of specific gene expression by nanomolar concentration of double-stranded dumbbell oligonucleotides. Nucleic Acids Res. 1993 Jul 25;21(15):3405–3411. doi: 10.1093/nar/21.15.3405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cooper C. L., Berrier A. L., Roman C., Calame K. L. Limited expression of C/EBP family proteins during B lymphocyte development. Negative regulator Ig/EBP predominates early and activator NF-IL-6 is induced later. J Immunol. 1994 Dec 1;153(11):5049–5058. [PubMed] [Google Scholar]
  13. Descombes P., Schibler U. A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Cell. 1991 Nov 1;67(3):569–579. doi: 10.1016/0092-8674(91)90531-3. [DOI] [PubMed] [Google Scholar]
  14. DiLorenzo T. P., Taichman L. B., Steinberg B. M. Replication and persistence of HPV DNA in cultured cells derived from laryngeal papillomas. Virology. 1992 Jan;186(1):148–153. doi: 10.1016/0042-6822(92)90068-z. [DOI] [PubMed] [Google Scholar]
  15. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Freytag S. O., Geddes T. J. Reciprocal regulation of adipogenesis by Myc and C/EBP alpha. Science. 1992 Apr 17;256(5055):379–382. doi: 10.1126/science.256.5055.379. [DOI] [PubMed] [Google Scholar]
  17. Gregori C., Kahn A., Pichard A. L. Competition between transcription factors HNF1 and HNF3, and alternative cell-specific activation by DBP and C/EBP contribute to the regulation of the liver-specific aldolase B promoter. Nucleic Acids Res. 1993 Feb 25;21(4):897–903. doi: 10.1093/nar/21.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Haas J. G., Ströbel M., Leutz A., Wendelgass P., Müller C., Sterneck E., Riethmüller G., Ziegler-Heitbrock H. W. Constitutive monocyte-restricted activity of NF-M, a nuclear factor that binds to a C/EBP motif. J Immunol. 1992 Jul 1;149(1):237–243. [PubMed] [Google Scholar]
  19. Hsu W., Chen-Kiang S. Convergent regulation of NF-IL6 and Oct-1 synthesis by interleukin-6 and retinoic acid signaling in embryonal carcinoma cells. Mol Cell Biol. 1993 Apr;13(4):2515–2523. doi: 10.1128/mcb.13.4.2515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hsu W., Kerppola T. K., Chen P. L., Curran T., Chen-Kiang S. Fos and Jun repress transcription activation by NF-IL6 through association at the basic zipper region. Mol Cell Biol. 1994 Jan;14(1):268–276. doi: 10.1128/mcb.14.1.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Isshiki H., Akira S., Sugita T., Nishio Y., Hashimoto S., Pawlowski T., Suematsu S., Kishimoto T. Reciprocal expression of NF-IL6 and C/EBP in hepatocytes: possible involvement of NF-IL6 in acute phase protein gene expression. New Biol. 1991 Jan;3(1):63–70. [PubMed] [Google Scholar]
  22. Katz S., Kowenz-Leutz E., Müller C., Meese K., Ness S. A., Leutz A. The NF-M transcription factor is related to C/EBP beta and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells. EMBO J. 1993 Apr;12(4):1321–1332. doi: 10.1002/j.1460-2075.1993.tb05777.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kinoshita S., Akira S., Kishimoto T. A member of the C/EBP family, NF-IL6 beta, forms a heterodimer and transcriptionally synergizes with NF-IL6. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1473–1476. doi: 10.1073/pnas.89.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kishimoto T., Akira S., Taga T. IL-6 receptor and mechanism of signal transduction. Int J Immunopharmacol. 1992 Apr;14(3):431–438. doi: 10.1016/0192-0561(92)90173-i. [DOI] [PubMed] [Google Scholar]
  25. Klampfer L., Lee T. H., Hsu W., Vilcek J., Chen-Kiang S. NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1. Mol Cell Biol. 1994 Oct;14(10):6561–6569. doi: 10.1128/mcb.14.10.6561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kunsch C., Lang R. K., Rosen C. A., Shannon M. F. Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6. J Immunol. 1994 Jul 1;153(1):153–164. [PubMed] [Google Scholar]
  27. Kyo S., Inoue M., Nishio Y., Nakanishi K., Akira S., Inoue H., Yutsudo M., Tanizawa O., Hakura A. NF-IL6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region. J Virol. 1993 Feb;67(2):1058–1066. doi: 10.1128/jvi.67.2.1058-1066.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lee Y. H., Yano M., Liu S. Y., Matsunaga E., Johnson P. F., Gonzalez F. J. A novel cis-acting element controlling the rat CYP2D5 gene and requiring cooperativity between C/EBP beta and an Sp1 factor. Mol Cell Biol. 1994 Feb;14(2):1383–1394. doi: 10.1128/mcb.14.2.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lin F. T., Lane M. D. Antisense CCAAT/enhancer-binding protein RNA suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3T3-L1 preadipocytes. Genes Dev. 1992 Apr;6(4):533–544. doi: 10.1101/gad.6.4.533. [DOI] [PubMed] [Google Scholar]
  30. Lin F. T., MacDougald O. A., Diehl A. M., Lane M. D. A 30-kDa alternative translation product of the CCAAT/enhancer binding protein alpha message: transcriptional activator lacking antimitotic activity. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9606–9610. doi: 10.1073/pnas.90.20.9606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Liu J. S., Park E. A., Gurney A. L., Roesler W. J., Hanson R. W. Cyclic AMP induction of phosphoenolpyruvate carboxykinase (GTP) gene transcription is mediated by multiple promoter elements. J Biol Chem. 1991 Oct 5;266(28):19095–19102. [PubMed] [Google Scholar]
  32. MacDougald O. A., Cornelius P., Lin F. T., Chen S. S., Lane M. D. Glucocorticoids reciprocally regulate expression of the CCAAT/enhancer-binding protein alpha and delta genes in 3T3-L1 adipocytes and white adipose tissue. J Biol Chem. 1994 Jul 22;269(29):19041–19047. [PubMed] [Google Scholar]
  33. Maran A., Amella C. A., Di Lorenzo T. P., Auborn K. J., Taichman L. B., Steinberg B. M. Human papillomavirus type 11 transcripts are present at low abundance in latently infected respiratory tissues. Virology. 1995 Oct 1;212(2):285–294. doi: 10.1006/viro.1995.1486. [DOI] [PubMed] [Google Scholar]
  34. McCaffery R. E., Jackson M. E. An element binding a C/EBP-related transcription factor contributes to negative regulation of the bovine papillomavirus type 4 long control region. J Gen Virol. 1994 Nov;75(Pt 11):3047–3056. doi: 10.1099/0022-1317-75-11-3047. [DOI] [PubMed] [Google Scholar]
  35. Mischoulon D., Rana B., Bucher N. L., Farmer S. R. Growth-dependent inhibition of CCAAT enhancer-binding protein (C/EBP alpha) gene expression during hepatocyte proliferation in the regenerating liver and in culture. Mol Cell Biol. 1992 Jun;12(6):2553–2560. doi: 10.1128/mcb.12.6.2553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mungal S., Steinberg B. M., Taichman L. B. Replication of plasmid-derived human papillomavirus type 11 DNA in cultured keratinocytes. J Virol. 1992 May;66(5):3220–3224. doi: 10.1128/jvi.66.5.3220-3224.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Natsuka S., Akira S., Nishio Y., Hashimoto S., Sugita T., Isshiki H., Kishimoto T. Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6. Blood. 1992 Jan 15;79(2):460–466. [PubMed] [Google Scholar]
  38. Nishio Y., Isshiki H., Kishimoto T., Akira S. A nuclear factor for interleukin-6 expression (NF-IL6) and the glucocorticoid receptor synergistically activate transcription of the rat alpha 1-acid glycoprotein gene via direct protein-protein interaction. Mol Cell Biol. 1993 Mar;13(3):1854–1862. doi: 10.1128/mcb.13.3.1854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Noonberg S. B., Garovoy M. R., Hunt C. A. Characteristics of oligonucleotide uptake in human keratinocyte cultures. J Invest Dermatol. 1993 Nov;101(5):727–731. doi: 10.1111/1523-1747.ep12371683. [DOI] [PubMed] [Google Scholar]
  40. Park E. A., Gurney A. L., Nizielski S. E., Hakimi P., Cao Z., Moorman A., Hanson R. W. Relative roles of CCAAT/enhancer-binding protein beta and cAMP regulatory element-binding protein in controlling transcription of the gene for phosphoenolpyruvate carboxykinase (GTP). J Biol Chem. 1993 Jan 5;268(1):613–619. [PubMed] [Google Scholar]
  41. Pope R. M., Leutz A., Ness S. A. C/EBP beta regulation of the tumor necrosis factor alpha gene. J Clin Invest. 1994 Oct;94(4):1449–1455. doi: 10.1172/JCI117482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rheinwald J. G., Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331–343. doi: 10.1016/s0092-8674(75)80001-8. [DOI] [PubMed] [Google Scholar]
  43. Ron D., Brasier A. R., McGehee R. E., Jr, Habener J. F. Tumor necrosis factor-induced reversal of adipocytic phenotype of 3T3-L1 cells is preceded by a loss of nuclear CCAAT/enhancer binding protein (C/EBP). J Clin Invest. 1992 Jan;89(1):223–233. doi: 10.1172/JCI115566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Scott L. M., Civin C. I., Rorth P., Friedman A. D. A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells. Blood. 1992 Oct 1;80(7):1725–1735. [PubMed] [Google Scholar]
  45. Sibbet G. J., Campo M. S. Multiple interactions between cellular factors and the non-coding region of human papillomavirus type 16. J Gen Virol. 1990 Nov;71(Pt 11):2699–2707. doi: 10.1099/0022-1317-71-11-2699. [DOI] [PubMed] [Google Scholar]
  46. Stein B., Cogswell P. C., Baldwin A. S., Jr Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction. Mol Cell Biol. 1993 Jul;13(7):3964–3974. doi: 10.1128/mcb.13.7.3964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Stephens J. M., Pekala P. H. Transcriptional repression of the C/EBP-alpha and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. Regulations is coordinate and independent of protein synthesis. J Biol Chem. 1992 Jul 5;267(19):13580–13584. [PubMed] [Google Scholar]
  48. Sterneck E., Müller C., Katz S., Leutz A. Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1 and NF-M, a myeloid specific, C/EBP-like factor. EMBO J. 1992 Jan;11(1):115–126. doi: 10.1002/j.1460-2075.1992.tb05034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Stoler M. H., Wolinsky S. M., Whitbeck A., Broker T. R., Chow L. T. Differentiation-linked human papillomavirus types 6 and 11 transcription in genital condylomata revealed by in situ hybridization with message-specific RNA probes. Virology. 1989 Sep;172(1):331–340. doi: 10.1016/0042-6822(89)90135-9. [DOI] [PubMed] [Google Scholar]
  50. Umek R. M., Friedman A. D., McKnight S. L. CCAAT-enhancer binding protein: a component of a differentiation switch. Science. 1991 Jan 18;251(4991):288–292. doi: 10.1126/science.1987644. [DOI] [PubMed] [Google Scholar]
  51. Wegner M., Cao Z., Rosenfeld M. G. Calcium-regulated phosphorylation within the leucine zipper of C/EBP beta. Science. 1992 Apr 17;256(5055):370–373. doi: 10.1126/science.256.5055.370. [DOI] [PubMed] [Google Scholar]
  52. Williams S. C., Cantwell C. A., Johnson P. F. A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. Genes Dev. 1991 Sep;5(9):1553–1567. doi: 10.1101/gad.5.9.1553. [DOI] [PubMed] [Google Scholar]

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