Abstract
It has recently been reported that c-myc is an inducible gene, regulated directly by growth signals which promote proliferation and expressed in a cell-cycle dependent manner1. Because various leukaemic cell lines express high levels of c-myc messenger RNA2, it was of interest to discover whether the gene could be down-regulated in these cells by a growth inhibitor such as interferon (IFN)3 We show here that in Daudi Burkitt's lymphoma cells, IFN-α produces a five- to sevenfold reduction in c-myc mRNA through a decreased rate of c-myc gene transcription. By isolating a growth-resistant Daudi cell variant that had escaped from this down-regulation, we provide the first clear link between reduction of c-myc mRNA and the IFN-mediated G0/G1 arrest characteristic of Daudi cells. Furthermore, by screening other cell lines, we demonstrate the heterogeneity of human leukaemic cells with respect to these criteria. Thus, IFN-α fails to reduce the c-myc mRNA and to change the cell-cycle distribution in HL-60 and U937 cells, although normal induction of other IFN-regulated activities takes place. The latter group of cells shows a decline in c-myc gene expression when they become arrested in the G0/G1 phase as part of their terminal differentiation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Kelly, K., Cochran, B. H., Stiles, C. D. & Leder, P. Cell 35, 603–610 (1983).
Westin, E. H. et al. Proc. natn. Acad. Sci. U.S.A. 79, 2490–2494 (1982).
Taylor-Papadimitriou, J. in Interferon Vol. 2 (ed. Gresser, I.) 13–46 (Academic, New York, 1980).
Collins, S. J., Ruscetti, F. W., Gallagher, R. E. & Gallo, R. C. Proc. natn. Acad. Sci. U.S.A. 75, 2458–2462 (1978).
Sundström, C. & Nilsson, K. Int. J. Cancer 7, 565–577 (1976).
Marks, P. A. & Rifkind, R. A. A. Rev. Biochem. 47, 419–448 (1978).
Klein, E. et al. Cancer Res. 28, 1300–1310 (1967).
Novick, D., Eshhar, Z. & Rubinstein, M. J. Immun. 129, 2244–2247 (1982).
Fellous, M. et al. Proc. natn. Acad. Sci. U.S.A. 79, 3081–3086 (1982).
Yarden, A., Shure-Gottlieb, H., Chebath, J., Revel, M. & Kimchi, A. EMBO J. 3, 969–973 (1984).
Merlin, G., Chebath, J., Benech, P., Metz, R. & Revel, M. Proc. natn. Acad. Sci. U.S.A. 80, 4904–4908 (1983).
Jonak, G. J. & Knight, E. Jr. Proc. natn. Acad. Sci. U.S.A. 81, 1747–1750 (1984).
Friedman-Einat, M., Revel, M. & Kimchi, A. Molec cell. Biol. 2, 1472–1480 (1982).
Bendori, R., Resnitzky, D. & Kimchi, A. FEBS Lett. 162, 384–389 (1983).
Dalla-Favera, R. et al. Proc. natn. Acad. Sci. U.S.A. 79, 6497–6501 (1982).
Cullen, M. H. & Capellaro, D. F. in Pulse-Cytophotometry: Proc. 3rd int. Symp. (ed. Lutz, D.) 643–657 (European Press, Ghent, 1978).
Sood, A. K., Pereira, D. & Weissman, S. M. Proc. natn. Acad. Sci. U.S.A. 78, 616–620 (1981).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Einat, M., Resnitzky, D. & Kimchi, A. Close link between reduction of c-myc expression by interferon and G0/G1 arrest. Nature 313, 597–600 (1985). https://doi.org/10.1038/313597a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/313597a0
- Springer Nature Limited
This article is cited by
-
Decoding the pathogenesis of Diamond–Blackfan anemia using single-cell RNA-seq
Cell Discovery (2022)
-
Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma
Nature Medicine (2019)
-
Covalent ISG15 conjugation to CHIP promotes its ubiquitin E3 ligase activity and inhibits lung cancer cell growth in response to type I interferon
Cell Death & Disease (2018)
-
Epstein–Barr virus: more than 50 years old and still providing surprises
Nature Reviews Cancer (2016)
-
Defining the mechanism by which IFN-β dowregulates c-myc expression in human melanoma cells: pivotal role for human polynucleotide phosphorylase (hPNPaseold-35)
Cell Death & Differentiation (2006)