Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jul 5;91(14):6433–6437. doi: 10.1073/pnas.91.14.6433

The POU domain protein Tst-1 and papovaviral large tumor antigen function synergistically to stimulate glia-specific gene expression of JC virus.

K Renner 1, H Leger 1, M Wegner 1
PMCID: PMC44216  PMID: 8022800

Abstract

Synergism between transcriptional activators is a powerful way of potentiating their function. Here we show that the glial POU domain protein Tst-1 (also known as Oct-6 and SCIP) and large tumor antigen (T antigen) synergistically increased transcription from both the early and the late promoters of papovavirus JC in glial cells. Synergism between both proteins did not require T-antigen-mediated DNA replication or direct binding of T antigen to the promoter. The ability of T antigen to functionally cooperate with Tst-1 was contained within its N-terminal region, shown by the fact that small tumor antigen (t antigen) could substitute for T antigen in transfection experiments. In addition to this functional synergism, a direct interaction between Tst-1 and T antigen was observed in vitro. Using deletion mutants of Tst-1 and T antigen, the POU domain of Tst-1 and the N-terminal region of T antigen were found to participate in this interaction. Because of the low levels of Tst-1 present in oligodendrocytes, synergism between Tst-1 and T antigen could be an important factor in establishing the lytic infection of oligodendrocytes by JC virus during the course of the fatal demyelinating disease progressive multifocal leukoencephalopathy.

Full text

PDF
6437

Images in this article

6434Image
on p.6434
6436Image
on p.6436
6436Image
on p.6436

Selected References

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

  1. Brady J., Khoury G. trans Activation of the simian virus 40 late transcription unit by T-antigen. Mol Cell Biol. 1985 Jun;5(6):1391–1399. doi: 10.1128/mcb.5.6.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Collarini E. J., Kuhn R., Marshall C. J., Monuki E. S., Lemke G., Richardson W. D. Down-regulation of the POU transcription factor SCIP is an early event in oligodendrocyte differentiation in vitro. Development. 1992 Sep;116(1):193–200. doi: 10.1242/dev.116.1.193. [DOI] [PubMed] [Google Scholar]
  3. DePamphilis M. L. Transcriptional elements as components of eukaryotic origins of DNA replication. Cell. 1988 Mar 11;52(5):635–638. doi: 10.1016/0092-8674(88)90398-4. [DOI] [PubMed] [Google Scholar]
  4. Fanning E. Simian virus 40 large T antigen: the puzzle, the pieces, and the emerging picture. J Virol. 1992 Mar;66(3):1289–1293. doi: 10.1128/jvi.66.3.1289-1293.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Gilinger G., Alwine J. C. Transcriptional activation by simian virus 40 large T antigen: requirements for simple promoter structures containing either TATA or initiator elements with variable upstream factor binding sites. J Virol. 1993 Nov;67(11):6682–6688. doi: 10.1128/jvi.67.11.6682-6688.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gruda M. C., Zabolotny J. M., Xiao J. H., Davidson I., Alwine J. C. Transcriptional activation by simian virus 40 large T antigen: interactions with multiple components of the transcription complex. Mol Cell Biol. 1993 Feb;13(2):961–969. doi: 10.1128/mcb.13.2.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hara Y., Rovescalli A. C., Kim Y., Nirenberg M. Structure and evolution of four POU domain genes expressed in mouse brain. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3280–3284. doi: 10.1073/pnas.89.8.3280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. He X., Gerrero R., Simmons D. M., Park R. E., Lin C. J., Swanson L. W., Rosenfeld M. G. Tst-1, a member of the POU domain gene family, binds the promoter of the gene encoding the cell surface adhesion molecule P0. Mol Cell Biol. 1991 Mar;11(3):1739–1744. doi: 10.1128/mcb.11.3.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. He X., Treacy M. N., Simmons D. M., Ingraham H. A., Swanson L. W., Rosenfeld M. G. Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature. 1989 Jul 6;340(6228):35–41. doi: 10.1038/340035a0. [DOI] [PubMed] [Google Scholar]
  12. Jiang D., Srinivasan A., Lozano G., Robbins P. D. SV40 T antigen abrogates p53-mediated transcriptional activity. Oncogene. 1993 Oct;8(10):2805–2812. [PubMed] [Google Scholar]
  13. Keller J. M., Alwine J. C. Analysis of an activatable promoter: sequences in the simian virus 40 late promoter required for T-antigen-mediated trans activation. Mol Cell Biol. 1985 Aug;5(8):1859–1869. doi: 10.1128/mcb.5.8.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Kristie T. M., LeBowitz J. H., Sharp P. A. The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein. EMBO J. 1989 Dec 20;8(13):4229–4238. doi: 10.1002/j.1460-2075.1989.tb08608.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Laurent B. C., Treich I., Carlson M. The yeast SNF2/SWI2 protein has DNA-stimulated ATPase activity required for transcriptional activation. Genes Dev. 1993 Apr;7(4):583–591. doi: 10.1101/gad.7.4.583. [DOI] [PubMed] [Google Scholar]
  17. Luo Y., Fujii H., Gerster T., Roeder R. G. A novel B cell-derived coactivator potentiates the activation of immunoglobulin promoters by octamer-binding transcription factors. Cell. 1992 Oct 16;71(2):231–241. doi: 10.1016/0092-8674(92)90352-d. [DOI] [PubMed] [Google Scholar]
  18. Lynch K. J., Frisque R. J. Identification of critical elements within the JC virus DNA replication origin. J Virol. 1990 Dec;64(12):5812–5822. doi: 10.1128/jvi.64.12.5812-5822.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Meijer D., Graus A., Grosveld G. Mapping the transactivation domain of the Oct-6 POU transcription factor. Nucleic Acids Res. 1992 May 11;20(9):2241–2247. doi: 10.1093/nar/20.9.2241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Meijer D., Graus A., Kraay R., Langeveld A., Mulder M. P., Grosveld G. The octamer binding factor Oct6: cDNA cloning and expression in early embryonic cells. Nucleic Acids Res. 1990 Dec 25;18(24):7357–7365. doi: 10.1093/nar/18.24.7357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mitchell P. J., Wang C., Tjian R. Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen. Cell. 1987 Sep 11;50(6):847–861. doi: 10.1016/0092-8674(87)90512-5. [DOI] [PubMed] [Google Scholar]
  23. Monuki E. S., Kuhn R., Weinmaster G., Trapp B. D., Lemke G. Expression and activity of the POU transcription factor SCIP. Science. 1990 Sep 14;249(4974):1300–1303. doi: 10.1126/science.1975954. [DOI] [PubMed] [Google Scholar]
  24. Monuki E. S., Weinmaster G., Kuhn R., Lemke G. SCIP: a glial POU domain gene regulated by cyclic AMP. Neuron. 1989 Dec;3(6):783–793. doi: 10.1016/0896-6273(89)90247-x. [DOI] [PubMed] [Google Scholar]
  25. Myers R. M., Rio D. C., Robbins A. K., Tjian R. SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. Cell. 1981 Aug;25(2):373–384. doi: 10.1016/0092-8674(81)90056-8. [DOI] [PubMed] [Google Scholar]
  26. Pomerantz J. L., Kristie T. M., Sharp P. A. Recognition of the surface of a homeo domain protein. Genes Dev. 1992 Nov;6(11):2047–2057. doi: 10.1101/gad.6.11.2047. [DOI] [PubMed] [Google Scholar]
  27. Rice P. W., Cole C. N. Efficient transcriptional activation of many simple modular promoters by simian virus 40 large T antigen. J Virol. 1993 Nov;67(11):6689–6697. doi: 10.1128/jvi.67.11.6689-6697.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rosenfeld M. G. POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev. 1991 Jun;5(6):897–907. doi: 10.1101/gad.5.6.897. [DOI] [PubMed] [Google Scholar]
  29. Schöler H. R., Ciesiolka T., Gruss P. A nexus between Oct-4 and E1A: implications for gene regulation in embryonic stem cells. Cell. 1991 Jul 26;66(2):291–304. doi: 10.1016/0092-8674(91)90619-a. [DOI] [PubMed] [Google Scholar]
  30. Sock E., Wegner M., Fortunato E. A., Grummt F. Large T-antigen and sequences within the regulatory region of JC virus both contribute to the features of JC virus DNA replication. Virology. 1993 Dec;197(2):537–548. doi: 10.1006/viro.1993.1627. [DOI] [PubMed] [Google Scholar]
  31. Sock E., Wegner M., Grummt F. DNA replication of human polyomavirus JC is stimulated by NF-I in vivo. Virology. 1991 May;182(1):298–308. doi: 10.1016/0042-6822(91)90673-y. [DOI] [PubMed] [Google Scholar]
  32. Stern S., Herr W. The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain. Genes Dev. 1991 Dec;5(12B):2555–2566. doi: 10.1101/gad.5.12b.2555. [DOI] [PubMed] [Google Scholar]
  33. Suzuki N., Rohdewohld H., Neuman T., Gruss P., Schöler H. R. Oct-6: a POU transcription factor expressed in embryonal stem cells and in the developing brain. EMBO J. 1990 Nov;9(11):3723–3732. doi: 10.1002/j.1460-2075.1990.tb07585.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tobler A., Schreiber E., Fontana A. The human Oct-6 POU transcription factor lacks the first 50 amino acids of its murine counterpart. Nucleic Acids Res. 1993 Feb 25;21(4):1043–1043. doi: 10.1093/nar/21.4.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wegner M., Drolet D. W., Rosenfeld M. G. POU-domain proteins: structure and function of developmental regulators. Curr Opin Cell Biol. 1993 Jun;5(3):488–498. doi: 10.1016/0955-0674(93)90015-i. [DOI] [PubMed] [Google Scholar]
  36. Wegner M., Drolet D. W., Rosenfeld M. G. Regulation of JC virus by the POU-domain transcription factor Tst-1: implications for progressive multifocal leukoencephalopathy. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4743–4747. doi: 10.1073/pnas.90.10.4743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wilson A. C., Patient R. K. DNA replication facilitates the action of transcriptional enhancers in transient expression assays. Nucleic Acids Res. 1993 Sep 11;21(18):4296–4304. doi: 10.1093/nar/21.18.4296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wun-Kim K., Simmons D. T. Mapping of helicase and helicase substrate-binding domains on simian virus 40 large T antigen. J Virol. 1990 May;64(5):2014–2020. doi: 10.1128/jvi.64.5.2014-2020.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Xue D., Tu Y., Chalfie M. Cooperative interactions between the Caenorhabditis elegans homeoproteins UNC-86 and MEC-3. Science. 1993 Sep 3;261(5126):1324–1328. doi: 10.1126/science.8103239. [DOI] [PubMed] [Google Scholar]
  40. Zhu J. Y., Rice P. W., Chamberlain M., Cole C. N. Mapping the transcriptional transactivation function of simian virus 40 large T antigen. J Virol. 1991 Jun;65(6):2778–2790. doi: 10.1128/jvi.65.6.2778-2790.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES