Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Sep;69(9):5843–5848. doi: 10.1128/jvi.69.9.5843-5848.1995

Transcriptional regulation of human JC polyomavirus promoters by cellular proteins YB-1 and Pur alpha in glial cells.

N N Chen 1, K Khalili 1
PMCID: PMC189456  PMID: 7637031

Abstract

Transcription of the human polyomavirus (JCV) genome is regulated by host cell proteins and the viral early protein, T antigen. A region called the lytic control element (LCE), located within the enhancer of JCV, is important for transcription of JCV early and late promoters. Earlier studies have led to the identification of two single-stranded DNA-binding proteins, YB-1 and Pur alpha, with the ability to interact with nucleotides on the early and late strands of LCE, respectively. Of particular interest is the notion that the unique interplay between these two cellular proteins and JCVT antigen determines their binding activities with the LCE. In this study, we employed a series of cotransfection experiments to evaluate the levels of transcription from JCV early and late promoters in the presence of YB-1, Pur alpha, and T antigen. Results from these studies indicated that Pur alpha stimulates JCV early and has little effect on the late promoter. Moreover, T antigen was able to decrease the induced level of early gene transcription by Pur alpha. On the other hand, the extent of transactivation of the viral late promoter by T antigen was reduced upon overexpression of Pur alpha in the transfected cells. These observations suggest that Pur alpha and T antigen exert an antagonistic effect on each other's regulatory action upon their responsive promoters. Of particular interest was the observation that YB-1 liberated T-antigen-induced late promoter activity from repression imposed by overexpression of pur alpha. Under similar conditions, overexpression of YB-1 showed no effect on the transcriptional activity of the early promoter in cells transfected with T-antigen- and Pur alpha-producing plasmids. On the basis of the data presented here and the previous binding results, a model is proposed which describes the potential role of Pur alpha, YB-1, and T antigen in differential expression of the viral genome during the lytic cycle.

Full Text

The Full Text of this article is available as a PDF (487.7 KB).

Selected References

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

  1. Ahmed S., Chowdhury M., Khalili K. Regulation of a human neurotropic virus promoter, JCVE: identification of a novel activator domain located upstream from the 98 bp enhancer promoter region. Nucleic Acids Res. 1990 Dec 25;18(24):7417–7423. doi: 10.1093/nar/18.24.7417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ahmed S., Rappaport J., Tada H., Kerr D., Khalili K. A nuclear protein derived from brain cells stimulates transcription of the human neurotropic virus promoter, JCVE, in vitro. J Biol Chem. 1990 Aug 15;265(23):13899–13905. [PubMed] [Google Scholar]
  3. Amemiya K., Traub R., Durham L., Major E. O. Interaction of a nuclear factor-1-like protein with the regulatory region of the human polyomavirus JC virus. J Biol Chem. 1989 Apr 25;264(12):7025–7032. [PubMed] [Google Scholar]
  4. Bergemann A. D., Ma Z. W., Johnson E. M. Sequence of cDNA comprising the human pur gene and sequence-specific single-stranded-DNA-binding properties of the encoded protein. Mol Cell Biol. 1992 Dec;12(12):5673–5682. doi: 10.1128/mcb.12.12.5673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang C. F., Tada H., Khalili K. The role of a pentanucleotide repeat sequence, AGGGAAGGGA, in the regulation of JC virus DNA replication. Gene. 1994 Oct 21;148(2):309–314. doi: 10.1016/0378-1119(94)90704-8. [DOI] [PubMed] [Google Scholar]
  6. Feigenbaum L., Khalili K., Major E., Khoury G. Regulation of the host range of human papovavirus JCV. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3695–3698. doi: 10.1073/pnas.84.11.3695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Frisque R. J., Bream G. L., Cannella M. T. Human polyomavirus JC virus genome. J Virol. 1984 Aug;51(2):458–469. doi: 10.1128/jvi.51.2.458-469.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  10. Kenney S., Natarajan V., Strike D., Khoury G., Salzman N. P. JC virus enhancer-promoter active in human brain cells. Science. 1984 Dec 14;226(4680):1337–1339. doi: 10.1126/science.6095453. [DOI] [PubMed] [Google Scholar]
  11. Kerr D. A., Chang C. F., Gordon J., Bjornsti M. A., Khalili K. Inhibition of human neurotropic virus (JCV) DNA replication in glial cells by camptothecin. Virology. 1993 Oct;196(2):612–618. doi: 10.1006/viro.1993.1517. [DOI] [PubMed] [Google Scholar]
  12. Kerr D., Khalili K. A recombinant cDNA derived from human brain encodes a DNA binding protein that stimulates transcription of the human neurotropic virus JCV. J Biol Chem. 1991 Aug 25;266(24):15876–15881. [PubMed] [Google Scholar]
  13. Khalili K., Brady J., Khoury G. Translational regulation of SV40 early mRNA defines a new viral protein. Cell. 1987 Feb 27;48(4):639–645. doi: 10.1016/0092-8674(87)90242-x. [DOI] [PubMed] [Google Scholar]
  14. Lashgari M. S., Tada H., Amini S., Khalili K. Regulation of JCVL promoter function: transactivation of JCVL promoter by JCV and SV40 early proteins. Virology. 1989 May;170(1):292–295. doi: 10.1016/0042-6822(89)90381-4. [DOI] [PubMed] [Google Scholar]
  15. Major E. O., Amemiya K., Tornatore C. S., Houff S. A., Berger J. R. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev. 1992 Jan;5(1):49–73. doi: 10.1128/cmr.5.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Raj G. V., Khalili K. Identification and characterization of a novel GGA/C-binding protein, GBP-i, that is rapidly inducible by cytokines. Mol Cell Biol. 1994 Dec;14(12):7770–7781. doi: 10.1128/mcb.14.12.7770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ranganathan P. N., Khalili K. The transcriptional enhancer element, kappa B, regulates promoter activity of the human neurotropic virus, JCV, in cells derived from the CNS. Nucleic Acids Res. 1993 Apr 25;21(8):1959–1964. doi: 10.1093/nar/21.8.1959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Small J. A., Scangos G. A., Cork L., Jay G., Khoury G. The early region of human papovavirus JC induces dysmyelination in transgenic mice. Cell. 1986 Jul 4;46(1):13–18. doi: 10.1016/0092-8674(86)90855-x. [DOI] [PubMed] [Google Scholar]
  19. Tada H., Khalili K. A novel sequence-specific DNA-binding protein, LCP-1, interacts with single-stranded DNA and differentially regulates early gene expression of the human neurotropic JC virus. J Virol. 1992 Dec;66(12):6885–6892. doi: 10.1128/jvi.66.12.6885-6892.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tada H., Lashgari M. S., Khalili K. Regulation of JCVL promoter function: evidence that a pentanucleotide "silencer" repeat sequence AGGGAAGGGA down-regulates transcription of the JC virus late promoter. Virology. 1991 Jan;180(1):327–338. doi: 10.1016/0042-6822(91)90037-c. [DOI] [PubMed] [Google Scholar]
  21. Tada H., Lashgari M., Rappaport J., Khalili K. Cell type-specific expression of JC virus early promoter is determined by positive and negative regulation. J Virol. 1989 Jan;63(1):463–466. doi: 10.1128/jvi.63.1.463-466.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES