Skip to main content
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
. 1992 May 1;89(9):3957–3961. doi: 10.1073/pnas.89.9.3957

Mutations in the bovine leukemia virus Tax protein can abrogate the long terminal repeat-directed transactivating activity without concomitant loss of transforming potential.

L Willems 1, C Grimonpont 1, H Heremans 1, N Rebeyrotte 1, G Chen 1, D Portetelle 1, A Burny 1, R Kettmann 1
PMCID: PMC525610  PMID: 1315045

Abstract

The bovine leukemia virus Tax protein transactivates gene expression directed by the viral long terminal repeat (LTR) and contributes to immortalization of primary cells. Theoretical analysis of the protein sequence revealed the presence of a putative zinc finger structure at its amino end. Selected mutations in that region completely abolished transactivation, demonstrating its importance for LTR-directed gene regulation. However, these mutations did not interfere with the ability of tax to bind zinc or to contribute to immortalization of primary cells. Thus, transactivation of bovine leukemia virus LTR and target cell transformation are independent functions of Tax and involve different functional domains of the protein.

Full text

PDF
3957

Images in this article

Selected References

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

  1. DeCaprio J. A., Ludlow J. W., Figge J., Shew J. Y., Huang C. M., Lee W. H., Marsilio E., Paucha E., Livingston D. M. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell. 1988 Jul 15;54(2):275–283. doi: 10.1016/0092-8674(88)90559-4. [DOI] [PubMed] [Google Scholar]
  2. Derse D. Bovine leukemia virus transcription is controlled by a virus-encoded trans-acting factor and by cis-acting response elements. J Virol. 1987 Aug;61(8):2462–2471. doi: 10.1128/jvi.61.8.2462-2471.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gitlin S. D., Lindholm P. F., Marriott S. J., Brady J. N. Transdominant human T-cell lymphotropic virus type I TAX1 mutant that fails to localize to the nucleus. J Virol. 1991 May;65(5):2612–2621. doi: 10.1128/jvi.65.5.2612-2621.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Inoue J., Seiki M., Taniguchi T., Tsuru S., Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J. 1986 Nov;5(11):2883–2888. doi: 10.1002/j.1460-2075.1986.tb04583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  7. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  8. Rice N. R., Stephens R. M., Couez D., Deschamps J., Kettmann R., Burny A., Gilden R. V. The nucleotide sequence of the env gene and post-env region of bovine leukemia virus. Virology. 1984 Oct 15;138(1):82–93. doi: 10.1016/0042-6822(84)90149-1. [DOI] [PubMed] [Google Scholar]
  9. Ruben S., Perkins A., Purcell R., Joung K., Sia R., Burghoff R., Haseltine W. A., Rosen C. A. Structural and functional characterization of human immunodeficiency virus tat protein. J Virol. 1989 Jan;63(1):1–8. doi: 10.1128/jvi.63.1.1-8.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sagata N., Yasunaga T., Tsuzuku-Kawamura J., Ohishi K., Ogawa Y., Ikawa Y. Complete nucleotide sequence of the genome of bovine leukemia virus: its evolutionary relationship to other retroviruses. Proc Natl Acad Sci U S A. 1985 Feb;82(3):677–681. doi: 10.1073/pnas.82.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Smith M. R., Greene W. C. Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes. Genes Dev. 1990 Nov;4(11):1875–1885. doi: 10.1101/gad.4.11.1875. [DOI] [PubMed] [Google Scholar]
  12. Smith M. R., Greene W. C. Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway. J Clin Invest. 1991 Sep;88(3):1038–1042. doi: 10.1172/JCI115364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  14. Srinivasan A., Peden K. W., Pipas J. M. The large tumor antigen of simian virus 40 encodes at least two distinct transforming functions. J Virol. 1989 Dec;63(12):5459–5463. doi: 10.1128/jvi.63.12.5459-5463.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Studier F. W., Rosenberg A. H., Dunn J. J., Dubendorff J. W. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. doi: 10.1016/0076-6879(90)85008-c. [DOI] [PubMed] [Google Scholar]
  16. Wigler M., Sweet R., Sim G. K., Wold B., Pellicer A., Lacy E., Maniatis T., Silverstein S., Axel R. Transformation of mammalian cells with genes from procaryotes and eucaryotes. Cell. 1979 Apr;16(4):777–785. doi: 10.1016/0092-8674(79)90093-x. [DOI] [PubMed] [Google Scholar]
  17. Willems L., Chen G., Portetelle D., Mamoun R., Burny A., Kettmann R. Structural and functional characterization of mutants of the bovine leukemia virus transactivator protein p34. Virology. 1989 Aug;171(2):615–618. doi: 10.1016/0042-6822(89)90633-8. [DOI] [PubMed] [Google Scholar]
  18. Willems L., Gegonne A., Chen G., Burny A., Kettmann R., Ghysdael J. The bovine leukemia virus p34 is a transactivator protein. EMBO J. 1987 Nov;6(11):3385–3389. doi: 10.1002/j.1460-2075.1987.tb02661.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Willems L., Heremans H., Chen G., Portetelle D., Billiau A., Burny A., Kettmann R. Cooperation between bovine leukaemia virus transactivator protein and Ha-ras oncogene product in cellular transformation. EMBO J. 1990 May;9(5):1577–1581. doi: 10.1002/j.1460-2075.1990.tb08277.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Willems L., Kettmann R., Burny A. The amino acid (157-197) peptide segment of bovine leukemia virus p34tax encompass a leucine-rich globally neutral activation domain. Oncogene. 1991 Jan;6(1):159–163. [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