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. 1990 May;64(5):2193–2201. doi: 10.1128/jvi.64.5.2193-2201.1990

Transcriptional regulation of early-response genes during polyomavirus infection.

G M Glenn 1, W Eckhart 1
PMCID: PMC249379  PMID: 1691311

Abstract

Infection of quiescent BALB/c 3T3 cells with polyomavirus leads to the biphasic accumulation of RNA from several early-response genes. The steady-state levels of RNA of c-fos, c-myc, and c-jun were detected at 0 to 1 and 12 to 30 h after infection but not at 6 h postinfection. Infections with mutant viruses suggest that in the context of a virus infection with other tumor (T) antigens present, large T and middle T antigens are dispensable for the effect and small t antigen is important for the regulation, perhaps in conjunction with large T or middle T antigens. These results are in agreement with those of Zullo et al. (Proc. Natl. Acad. Sci. USA 84:1210-1214). We have further found that this regulation occurs in NIH 3T3 cells and primary mouse embryo fibroblasts. DNA synthesis is not required for this effect. Half-lives of c-fos, c-myc, and c-jun were similarly short at both early and late times after infection, as determined by dactinomycin chase. The regulation of expression occurs at the transcriptional level. Nuclear run-on experiments showed increased rates of transcription both early and late after infection. Also, the polyomavirus early region can transactivate the c-fos promoter in transient transfection assays.

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Selected References

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

  1. Asselin C., Gelinas C., Bastin M. Role of the three polyoma virus early proteins in tumorigenesis. Mol Cell Biol. 1983 Aug;3(8):1451–1459. doi: 10.1128/mcb.3.8.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asselin C., Gélinas C., Branton P. E., Bastin M. Polyoma middle T antigen requires cooperation from another gene to express the malignant phenotype in vivo. Mol Cell Biol. 1984 Apr;4(4):755–760. doi: 10.1128/mcb.4.4.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berger H., Wintersberger E. Polyomavirus small T antigen enhances replication of viral genomes in 3T6 mouse fibroblasts. J Virol. 1986 Nov;60(2):768–770. doi: 10.1128/jvi.60.2.768-770.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bikel I., Mamon H., Brown E. L., Boltax J., Agha M., Livingston D. M. The t-unique coding domain is important to the transformation maintenance function of the simian virus 40 small t antigen. Mol Cell Biol. 1986 Apr;6(4):1172–1178. doi: 10.1128/mcb.6.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bikel I., Montano X., Agha M. E., Brown M., McCormack M., Boltax J., Livingston D. M. SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen. Cell. 1987 Jan 30;48(2):321–330. doi: 10.1016/0092-8674(87)90435-1. [DOI] [PubMed] [Google Scholar]
  6. Brenner D. A., O'Hara M., Angel P., Chojkier M., Karin M. Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. Nature. 1989 Feb 16;337(6208):661–663. doi: 10.1038/337661a0. [DOI] [PubMed] [Google Scholar]
  7. Carmichael G. G., Benjamin T. L. Identification of DNA sequence changes leading to loss of transforming ability in polyoma virus. J Biol Chem. 1980 Jan 10;255(1):230–235. [PubMed] [Google Scholar]
  8. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cherington V., Morgan B., Spiegelman B. M., Roberts T. M. Recombinant retroviruses that transduce individual polyoma tumor antigens: effects on growth and differentiation. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4307–4311. doi: 10.1073/pnas.83.12.4307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  11. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  12. Della Valle G., Fenton R. G., Basilico C. Polyoma large T antigen regulates the integration of viral DNA sequences into the genome of transformed cells. Cell. 1981 Feb;23(2):347–355. doi: 10.1016/0092-8674(81)90130-6. [DOI] [PubMed] [Google Scholar]
  13. Deschamps J., Meijlink F., Verma I. M. Identification of a transcriptional enhancer element upstream from the proto-oncogene fos. Science. 1985 Dec 6;230(4730):1174–1177. doi: 10.1126/science.3865371. [DOI] [PubMed] [Google Scholar]
  14. Draetta G., Beach D., Moran E. Synthesis of p34, the mammalian homolog of the yeast cdc2+/CDC28 protein kinase, is stimulated during adenovirus-induced proliferation of primary baby rat kidney cells. Oncogene. 1988 Jun;2(6):553–557. [PubMed] [Google Scholar]
  15. Eckhart W. Complementation and transformation by temperature-sensitive mutants of polyoma virus. Virology. 1969 May;38(1):120–125. doi: 10.1016/0042-6822(69)90133-0. [DOI] [PubMed] [Google Scholar]
  16. Francke B., Eckhart W. Polyoma gene function required for viral DNA synthesis. Virology. 1973 Sep;55(1):127–135. doi: 10.1016/s0042-6822(73)81014-1. [DOI] [PubMed] [Google Scholar]
  17. Fujii M., Shalloway D., Verma I. M. Gene regulation by tyrosine kinases: src protein activates various promoters, including c-fos. Mol Cell Biol. 1989 Jun;9(6):2493–2499. doi: 10.1128/mcb.9.6.2493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Garcea R. L., Talmage D. A., Harmatz A., Freund R., Benjamin T. L. Separation of host range from transformation functions of the hr-t gene of polyomavirus. Virology. 1989 Feb;168(2):312–319. doi: 10.1016/0042-6822(89)90271-7. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Groudine M., Peretz M., Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. doi: 10.1128/mcb.1.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Heike T., Miyatake S., Yoshida M., Arai K., Arai N. Bovine papilloma virus encoded E2 protein activates lymphokine genes through DNA elements, distinct from the consensus motif, in the long control region of its own genome. EMBO J. 1989 May;8(5):1411–1417. doi: 10.1002/j.1460-2075.1989.tb03522.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ito Y., Spurr N., Dulbecco R. Characterization of polyoma virus T antigen. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1259–1263. doi: 10.1073/pnas.74.3.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kaplan D. R., Whitman M., Schaffhausen B., Raptis L., Garcea R. L., Pallas D., Roberts T. M., Cantley L. Phosphatidylinositol metabolism and polyoma-mediated transformation. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3624–3628. doi: 10.1073/pnas.83.11.3624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kingston R. E., Cowie A., Morimoto R. I., Gwinn K. A. Binding of polyomavirus large T antigen to the human hsp70 promoter is not required for trans activation. Mol Cell Biol. 1986 Sep;6(9):3180–3190. doi: 10.1128/mcb.6.9.3180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kruijer W., Cooper J. A., Hunter T., Verma I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. doi: 10.1038/312711a0. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Liu H. T., Baserga R., Mercer W. E. Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum. Mol Cell Biol. 1985 Nov;5(11):2936–2942. doi: 10.1128/mcb.5.11.2936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Loeken M., Bikel I., Livingston D. M., Brady J. trans-activation of RNA polymerase II and III promoters by SV40 small t antigen. Cell. 1988 Dec 23;55(6):1171–1177. doi: 10.1016/0092-8674(88)90261-9. [DOI] [PubMed] [Google Scholar]
  29. Martens I., Nilsson S. A., Linder S., Magnusson G. Mutational analysis of polyomavirus small-T-antigen functions in productive infection and in transformation. J Virol. 1989 May;63(5):2126–2133. doi: 10.1128/jvi.63.5.2126-2133.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Parnes J. R., Seidman J. G. Structure of wild-type and mutant mouse beta 2-microglobulin genes. Cell. 1982 Jun;29(2):661–669. doi: 10.1016/0092-8674(82)90182-9. [DOI] [PubMed] [Google Scholar]
  32. Rassoulzadegan M., Naghashfar Z., Cowie A., Carr A., Grisoni M., Kamen R., Cuzin F. Expression of the large T protein of polyoma virus promotes the establishment in culture of "normal" rodent fibroblast cell lines. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4354–4358. doi: 10.1073/pnas.80.14.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sassone-Corsi P., Borrelli E. Promoter trans-activation of protooncogenes c-fos and c-myc, but not c-Ha-ras, by products of adenovirus early region 1A. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6430–6433. doi: 10.1073/pnas.84.18.6430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stanton L. W., Watt R., Marcu K. B. Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature. 1983 Jun 2;303(5916):401–406. doi: 10.1038/303401a0. [DOI] [PubMed] [Google Scholar]
  35. Stoker M., Dulbecco R. Abortive transformation by the Tsa mutant of polyoma virus. Nature. 1969 Jul 26;223(5204):397–398. doi: 10.1038/223397a0. [DOI] [PubMed] [Google Scholar]
  36. Templeton D., Eckhart W. Mutation causing premature termination of the polyoma virus medium T antigen blocks cell transformation. J Virol. 1982 Mar;41(3):1014–1024. doi: 10.1128/jvi.41.3.1014-1024.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Templeton D., Simon S., Eckhart W. Truncated forms of the polyomavirus middle T antigen can substitute for the small T antigen in lytic infection. J Virol. 1986 Jan;57(1):367–370. doi: 10.1128/jvi.57.1.367-370.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Treisman R., Novak U., Favaloro J., Kamen R. Transformation of rat cells by an altered polyoma virus genome expressing only the middle-T protein. Nature. 1981 Aug 13;292(5824):595–600. doi: 10.1038/292595a0. [DOI] [PubMed] [Google Scholar]
  39. Whitman M., Kaplan D. R., Schaffhausen B., Cantley L., Roberts T. M. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature. 1985 May 16;315(6016):239–242. doi: 10.1038/315239a0. [DOI] [PubMed] [Google Scholar]
  40. Zerler B., Roberts R. J., Mathews M. B., Moran E. Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products. Mol Cell Biol. 1987 Feb;7(2):821–829. doi: 10.1128/mcb.7.2.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zullo J., Stiles C. D., Garcea R. L. Regulation of c-myc and c-fos mRNA levels by polyomavirus: distinct roles for the capsid protein VP1 and the viral early proteins. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1210–1214. doi: 10.1073/pnas.84.5.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

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