Abstract
There is increasing evidence that at least some of the cellular homologues to retroviral oncogenes (c-onc or proto-oncogenes) are directly linked to the control of cell growth (for a review see ref. 1). Among these, c-myc, the cellular homologue to the avian myelocytomatosis virus (MC29) oncogene, has been shown to express high levels of mRNA during early G0/G1 phase after mitogenic stimulation of T lymphocytes2 by concanavalin A or of fibroblasts by platelet-derived growth factor (PDGF)2 or serum3. An attractive model proposed for this regulation is that the c-myc gene is strongly repressed in cells arrested in the G0 phase of the cell cycle by a growth factor-sensitive represser4. We have investigated an alternative model of post-transcriptional regulation. This latter model leads to two testable predictions. First, that c-myc mRNA should be unusually unstable, which we have confirmed5. And second, that there would be a high level of constitutive expression, a situation opposite to that implied by the represser model. Here we report that c-myc gene is indeed transcribed at a high rate in G0-arrested chinese hamster lung fibroblasts, although the level of mature c-myc mRNA is barely detectable. The early and dramatic increase in c-myc mRNA levels when these resting cells are stimulated by growth factors is not accompanied by any appreciable change in the transcription rate of c-myc gene. Taken together these findings support a model of post-transcriptional regulation of c-myc expression at the level of mRNA degradation.
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References
Land, H., Parada, L. F. & Weinberg, R. A. Science 222, 771–778 (1983).
Kelly, K., Cochran, B. H., Stiles, C. D. & Leder, P. Cell 35, 603–610 (1983).
Campisi, J., Gray, H. E., Pardee, A. B., Dean, M. & Sonensheim, G. E. Cell 36, 241–247 (1984).
Rabbits, T. H., Forster, A., Hamlyn, P. & Baer, R. Nature 309, 592–597 (1984).
Dani, Ch. et al. Proc. natn. Acad. Aci. U.S.A. 81, 7046–7050 (1984).
Bernard, O., Cory, S., Gerondakis, S., Webb, E. & Adams, J. M. EMBO J. 2, 2375–2383 (1983).
Nishikura, K. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4822–4826 (1983).
Taub, R. et al. Cell 36, 339–348 (1984).
Leder, P. et al. Science 222, 765–771 (1983).
Pouysségur, J., Franchi, A. & Silvestre, P. Nature 287, 445–447 (1980).
Pouysségur, J., Chambard, J. C., Franchi, A., Paris, S. & Van-Obberghen-Schilling, E. Proc. natn. Acad. Sci U.S.A. 79, 3935–3939 (1982).
Fort, Ph. et al. Nucleic Acids Res. 13, 1431–1442 (1985).
Greenberg, M. E. & Ziff, E. B. Nature 311, 433–438 (1984).
Kruijer, W., Cooper, J. A., Hunter, T. & Verma, I. M. Nature 312, 711–716 (1984).
Müller, R., Bravo, R. & Burckhardt, Nature 312, 716–720 (1984).
Schibler, U., Hagenbüchle, O., Wellauer, P. K. & Pittet, A. C. Cell 33, 501–508 (1983).
Marcu, K. B. et al. Proc. natn. Acad. Sci. U.S.A. 80, 519–523 (1983).
Miller, A. D., Curran, T. & Verma, I. M. Cell 36, 51–60 (1984).
Alonso, S., Minty, A., Bourlet, Y. & Buckingham, M. J. molec. Evol. (submitted).
Piechaczyk, M. et al. Nucleic Acids Res. 12, 6951–6963 (1984).
Blanchard, J. M., Brissac, C. & Jeanteur, Ph. Proc. natn. Acad. Sci. U.S.A. 71, 1882–1886 (1974).
Milhaud, P., Blanchard, J. M. & Jeanteur, Ph. Biochimie 60, 1343–1346 (1978).
Siebenlist, U., Hennighausen, L., Battey, J. & Leder, Ph. Cell 37, 381–391 (1984).
Groudine, M. & Casimir, C. Nucleic Acids Res. 12, 1427–1446 (1984).
Cleveland, D. W. & Havercroft, J. C. J. cell. Phys. 97, 919–924 (1983).
Leys, E. J., Crouse, G. F. & Kellems, R. E. J. cell Biol. 99, 180–187 (1984).
Bantle, J. A., Maxwell, I. M. & Hahn, W. E. Analyt. Biochem. 72, 413–427 (1976).
Thomas, P. S. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).
Leprince, D. et al. EMBO J. 2, 1073–1078 (1983).
Hassouna, N., Michot, B. & Bachellerie, J. P. Nucleic Acids Res. 12, 3563–3583 (1984).
Jonak, G. J. & Knight, E. Proc. natn. Acad. Sci. U.S.A. 81, 1747–1750 (1984).
Dani, Ch. et al. Proc. natn. Acad. Sci. U.S.A. 82, 4896–4899 (1985).
Piechaczyk, M. et al. Cell (in the press).
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Blanchard, JM., Piechaczyk, M., Dani, C. et al. c-myc gene is transcribed at high rate in G0-arrested fibroblasts and is post-transcriptionally regulated in response to growth factors. Nature 317, 443–445 (1985). https://doi.org/10.1038/317443a0
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DOI: https://doi.org/10.1038/317443a0
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