Transcription of the human polyomavirus JC virus (JCV) genome is regulated by cellular proteins and the large tumour (T) antigen. Earlier studies led to the identification of nuclear factor-1 (NF-1)-binding sites in the JCV enhancer by DNase I protection assays of extracts from retinoic acid (RA)-differentiated P19 embryonal carcinoma (EC) cells. In this study, a cDNA clone that encodes a protein capable of binding to the JCV NF-1 sites was isolated from an RA-differentiated EC cell cDNA library. Sequence analysis revealed that the cDNA isolated was identical to the previously described Bcl-2-interacting protein BAG-1 (Bcl-2-associated athano gene-1). Results from RNA studies indicated that BAG-1 is expressed in several cell types. Co-transfection of a recombinant BAG-1 expression plasmid with JCV promoters indicated that BAG-1 stimulates transcription of the JCV promoter and to a lesser extent the JCV promoter. Mutations in the NF-1 sites in the JCV promoter eliminated the activation by BAG-1. Thus, BAG-1 is a novel transcription factor that may play a role in JCV expression.


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  1. Ahmed, S., Chowdhury, M. & Khalili, K.(1990). 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 Research 18, 7417-7423.[CrossRef] [Google Scholar]
  2. Bardelli, A., Longati, P., Albero, D., Goruppi, S., Schneider, C., Ponzetto, C. & Comoglio, P. M.(1996). HGF receptor associates with the anti-apoptotic protein BAG-1 and prevents cell death.EMBO Journal 15, 6205-6212. [Google Scholar]
  3. Devireddy, L. R. (1995).Characterization of a cDNA encoding a novel transcription factor regulating expression of human neurotropic JC virus. MSc thesis, Memorial University of Newfoundland, St John’s, Newfoundland, Canada.
  4. Frisque, R. J., Bream, G. L. & Cannella, M. T.(1984). Human polyomavirus JC virus genome.Journal of Virology 51, 458-469. [Google Scholar]
  5. Froesch, B. A., Takayama, S. & Reed, J. C.(1998). BAG-1L protein enhances androgen receptor function.Journal of Biological Chemistry 273, 11660-11666.[CrossRef] [Google Scholar]
  6. Froesch, B. A., Aime-Sempe, C., Leber, B., Andrews, D. & Reed, J. C.(1999). Inhibition of p53 transcriptional activity by Bcl-2 requires its membrane-anchoring domain.Journal of Biological Chemistry 274, 6469-6475.[CrossRef] [Google Scholar]
  7. Henson, J. W., Saffer, J. & Furneaux, H.(1992). The transcription factor Sp1 binds to the JC virus promoter and is selectively expressed in glial cells in human brain.Annals of Neurology 32, 72-77.[CrossRef] [Google Scholar]
  8. Kenney, S., Natarajan, V., Strike, D., Khoury, G. & Salzman, N. P.(1984). JC virus enhancer-promoter active in human brain cells.Science 226, 1337-1339.[CrossRef] [Google Scholar]
  9. Khalili, K., Rappaport, J. & Khoury, G.(1988). Nuclear factors in human brain cells bind specifically to the JCV regulatory region.EMBO Journal 7, 1205-1210. [Google Scholar]
  10. Kullmann, M., Schneikert, J., Moll, J., Heck, S., Zeiner, M., Gehring, U. & Cato, A. C.(1998). RAP46 is a negative regulator of glucocorticoid receptor action and hormone-induced apoptosis.Journal of Biological Chemistry 273, 14620-14625.[CrossRef] [Google Scholar]
  11. Kumar, K. U. (1994).Transcriptional regulation of human JC virus. PhD thesis, Memorial University of Newfoundland, St John’s, Newfoundland, Canada.
  12. Kumar, K. U., Pater, A. & Pater, M. M.(1993). Human JC virus perfect palindromic nuclear factor 1-binding sequences important for glial cell-specific expression in differentiating embryonal carcinoma cells.Journal of Virology 67, 572-576. [Google Scholar]
  13. Liu, R., Takayama, S., Zheng, Y., Froesch, B., Chen, G. Q., Zhang, X., Reed, J. C. & Zhang, X. K.(1998). Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells.Journal of Biological Chemistry 273, 16985-16992.[CrossRef] [Google Scholar]
  14. Major, E. O., Amemiya, K., Tornatore, C. S., Houff, S. A. & Berger, J. R. (1992). Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.Clinical Microbiology Reviews 5, 49-73. [Google Scholar]
  15. Matsuzawa, S., Takayama, S., Froesch, B. A., Zapata, J. M. & Reed, J. C. (1998). p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1.EMBO Journal 17, 2736-2747.[CrossRef] [Google Scholar]
  16. Nakshatri, H., Pater, A. & Pater, M. M. (1990). Activity and enhancer binding factors for JC virus regulatory elements in differentiating embryonal carcinoma cells.Virology 177, 784-789.[CrossRef] [Google Scholar]
  17. Nakshatri, H., Pater, M. M. & Pater, A. (1991). Activity and enhancer binding factors for BK virus regulatory elements in differentiating embryonal carcinoma cells.Virology 183, 374-380.[CrossRef] [Google Scholar]
  18. Packham, G., Brimmell, M. & Cleveland, J. L. (1997). Mammalian cells express two differently localized Bag-1 isoforms generated by alternative translation initiation.Biochemical Journal 328, 807-813. [Google Scholar]
  19. Raj, G. V. & Khalili, K. (1995). Transcriptional regulation: lessons from the human neurotropic polyomavirus, JCV.Virology 213, 283-291.[CrossRef] [Google Scholar]
  20. Tada, H., Lashgari, M., Rappaport, J. & Khalili, K. (1989). Cell type-specific expression of JC virus early promoter is determined by positive and negative regulation.Journal of Virology 63, 463-466. [Google Scholar]
  21. Takayama, S., Sato, T., Krajewski, S., Kochel, K., Irie, S., Millan, J. A. & Reed, J. C. (1995). Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity.Cell 80, 279-284.[CrossRef] [Google Scholar]
  22. Takayama, S., Krajewski, S., Krajewska, M., Kitada, S., Zapata, J. M., Kochel, K., Knee, D., Scudiero, D., Tudor, G., Miller, G. J., Miyashita, T., Yamada, M. & Reed, J. C. (1998). Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines.Cancer Research 58, 3116-3131. [Google Scholar]
  23. Vinson, C. R., LaMarco, K. L., Johnson, P. F., Landschulz, W. H. & McKnight, S. L. (1988). In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage.Genes & Development 2, 801-806.[CrossRef] [Google Scholar]
  24. Wang, H. G. & Reed, J. C. (1998). Bcl-2, Raf-1 and mitochondrial regulation of apoptosis.Biofactors 8, 13-16.[CrossRef] [Google Scholar]
  25. Wang, H. G., Takayama, S., Rapp, U. R. & Reed, J. C. (1996). Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1.Proceedings of the National Academy of Sciences, USA 93, 7063-7068.[CrossRef] [Google Scholar]
  26. Weber, T. & Major, E. O. (1997). Progressive multifocal leukoencephalopathy: molecular biology, pathogenesis and clinical impact.Intervirology 40, 98-111.[CrossRef] [Google Scholar]
  27. Wegner, M., Drolet, D. W. & Rosenfeld, M. G. (1993). Regulation of JC virus by the POU-domain transcription factor Tst-1: implications for progressive multifocal leukoencephalopathy.Proceedings of the National Academy of Sciences, USA 90, 4743-4747.[CrossRef] [Google Scholar]

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