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Regulation of lymphocyte mitogenesis by (2′–5′) oligo-isoadenylate

Abstract

Interferon has been reported to affect cell proliferation in various tumour and normal cell cultures1. In human cells, the anti-growth effect of Interferon is under the control of chromosome 21, like the antiviral effect2,3, and the two activities appear to reside in the same glycoprotein4. In synchronised fibroblast cultures Interferon inhibited DNA synthesis by blocking initiations of DNA replication5,6. Another system in which the inhibitory effect of interferon on DNA synthesis was particularly clear is lymphocyte mitogenesis. In lymphocytes stimulated by lectin mitogens or allogeneic cells, interferon inhibits DNA synthesis, and the RNA and protein synthesis observed before the S phase of the cell cycle7–9. In interferon-treated ceUs, several enzymes are induced, including the (2′–5′) oligo-isoadenylate [oligo(A)] synthetase E, which polymerises ATP into a series of oligonucleotides of general structure ppp(A2′p)n5′A (refs 10–12). The (2′–5′) oligonucleotides inhibit protein synthesis when added to cell-free systems10–12 or hypotonically permeabilised cells13, and the induction of (2′–5′) oligo(A) synthetase was correlated with the antiviral action of interferon14,15. In the present work, the involvement of this enzyme in the antigrowth effect of interferon was studied. We show that addition of the (2′–5′) oligo(A)nucleotides to the culture medium of intact lymphocytes mimics the antimitogenic effect of interferon. Experiments with lymphocyte extracts show that, while interferon increases the (2′–5′)oligo(A) synthetase E, the mitogenic stimulus of concanavalin A leads to a decrease in (2′–5′) oligo(A) accumulation.

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References

  1. Gresser, I. & Tovey, M. G. Biochim biophys. Acta 516, 231–247 (1978).

    CAS  PubMed  Google Scholar 

  2. Cupples, C. G. & Tan, Y. H. Nature 267, 165–167 (1977).

    Article  ADS  CAS  Google Scholar 

  3. Gurari-Rotman, D. et al. FEBS Lett. 94, 187–190 (1978).

    Article  CAS  Google Scholar 

  4. Knight, E. Nature 262, 302–303 (1976).

    Article  ADS  CAS  Google Scholar 

  5. Sokawa, Y., Watanabe, Y., Watanabe, Y. & Kawade, Y. Nature 268, 236–238 (1977).

    Article  ADS  CAS  Google Scholar 

  6. Balkwill, F. R. & Taylor-Papadimitriou, J. Nature 274, 798–800 (1978).

    Article  ADS  CAS  Google Scholar 

  7. Lindahl-Magnusson, P., Leary, P. & Gresser, I. Nature new Biol. 237, 120–121 (1972).

    Article  CAS  Google Scholar 

  8. Pacheco, D. et al. Annls Immun. (Inst. Pasteur) 127 C, 163–171 (1976).

    Google Scholar 

  9. Weinstein, Y., Brodeur, B. R., Melmon, K. L. & Merigan, T. C. Immunology 33, 313–319 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Kerr, I. K. & Brown, R. E. Proc. natn. Acad. Sci. U.S.A. 75, 256–260 (1978).

    Article  ADS  CAS  Google Scholar 

  11. Ball, L. A. & White, C. N. Proc. natn. Acad. Sci. U.S.A. 75, 1167–1171 (1978).

    Article  ADS  CAS  Google Scholar 

  12. Zilberstein, A., Kimchi, A., Schmidt, A. & Revel, M. Proc. natn. Acad. Sci. U.S.A. 75, 4734–4738 (1978).

    Article  ADS  CAS  Google Scholar 

  13. Williams, B. R. G. & Kerr, I. M. Nature 276, 88–89 (1978).

    Article  ADS  CAS  Google Scholar 

  14. Kimchi, A., Shulman, L., Schmidt, A., Chernajovsky, Y., Fradin, A. & Revel, M. Proc. natn. Acad. Sci. U.S.A. 76, 3208–3212 (1979).

    Article  ADS  CAS  Google Scholar 

  15. Baglioni, C., Maroney, P. A. & West, D. K. Biochemistry 18, 1765–1768 (1979).

    Article  CAS  Google Scholar 

  16. Luftig, R. B. et al. J. Virol. 23, 799–810 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Revel, M. in Regulation of Macromolecular Synthesis by Low Molecular Weight Mediators (eds Koch, G. & Richter, D.) (Academic, New York, in the press).

  18. Sela, B. & Gurari-Rotman, D. Biochem. biophys. Res. Commun. 84, 550–556 (1978).

    Article  CAS  Google Scholar 

  19. Schmidt, A. et al. Proc. natn. Acad. Sci. U.S.A. 76, 4788–4792 (1979).

    Article  ADS  CAS  Google Scholar 

  20. Schmidt, A. et al. FEBS Lett. 95, 257–264 (1978).

    Article  CAS  Google Scholar 

  21. Farrell, P. J. et al. Proc. natn. Acad. Sci. U.S.A. 75, 5893–5897 (1978).

    Article  ADS  CAS  Google Scholar 

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Kimchi, A., Shure, H. & Revel, M. Regulation of lymphocyte mitogenesis by (2′–5′) oligo-isoadenylate. Nature 282, 849–851 (1979). https://doi.org/10.1038/282849a0

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