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. 1986 Aug 1;237(3):871–876. doi: 10.1042/bj2370871

Inhibition of cell proliferation by interferons. Relative contributions of changes in protein synthesis and breakdown to growth control of human lymphoblastoid cells.

M A McNurlan, M J Clemens
PMCID: PMC1147069  PMID: 2432876

Abstract

Treatment of the Daudi line of human lymphoblastoid cells with concentrations of human interferons within the physiological range progressively inhibits cell proliferation over 1-4 days. Rigorous measurement of the overall rate of protein synthesis during this period, using a concentration of [3H]phenylalanine sufficient to equalize the specific radioactivity of intracellular and extracellular precursor pools, shows that protein synthesis becomes progressively inhibited as the growth inhibition develops. There is a strong correlation between inhibition of amino acid incorporation and inhibition of cell proliferation. In contrast, we find no evidence for any increase in protein degradation rate under these conditions. These results suggest that interferon treatment of susceptible cells can inhibit protein synthesis even in the absence of virus infection and that this inhibition is of a sufficient magnitude to account for the anti-proliferative effect.

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Selected References

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

  1. Adams A., Strander H., Cantell K. Sensitivity of the Epstein-Barr virus transformed human lymphoid cell lines to interferon. J Gen Virol. 1975 Aug;28(2):207–217. doi: 10.1099/0022-1317-28-2-207. [DOI] [PubMed] [Google Scholar]
  2. Airhart J., Kelley J., Brayden J. E., Low R. B., Stirewalt W. S. An ultramicro method of amino acid analysis: application to studies of protein metabolism in cultured cells. Anal Biochem. 1979 Jul 1;96(1):45–55. doi: 10.1016/0003-2697(79)90552-9. [DOI] [PubMed] [Google Scholar]
  3. Ballard F. J. Regulation of protein accumulation in cultured cells. Biochem J. 1982 Nov 15;208(2):275–287. doi: 10.1042/bj2080275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brouty-Boyé D., Macieira-Coelho A., Fiszman M., Gresser I. Interferon and cell division. 8. Effect of interferon on macromolecular synthesis in L1210 Cells in vitro. Int J Cancer. 1973 Jul 15;12(1):250–258. doi: 10.1002/ijc.2910120126. [DOI] [PubMed] [Google Scholar]
  5. Castor L. N. Responses of protein synthesis and degradation in growth control of WI-38 cells. J Cell Physiol. 1977 Sep;92(3):457–467. doi: 10.1002/jcp.1040920313. [DOI] [PubMed] [Google Scholar]
  6. Clemens M. J., McNurlan M. A., Moore G., Tilleray V. J. Regulation of protein synthesis in lymphoblastoid cells during inhibition of cell proliferation by human interferons. FEBS Lett. 1984 Jun 4;171(1):111–116. doi: 10.1016/0014-5793(84)80469-x. [DOI] [PubMed] [Google Scholar]
  7. Clemens M. J., McNurlan M. A. Regulation of cell proliferation and differentiation by interferons. Biochem J. 1985 Mar 1;226(2):345–360. doi: 10.1042/bj2260345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clemens M. J., Tilleray V. J. Inhibition of polypeptide chain initiation in Daudi cells by interferons. Evidence that activity of initiation factor eIF-2 and availability of mRNA are unimpaired. Biochem J. 1986 Aug 1;237(3):877–884. doi: 10.1042/bj2370877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fuse A., Kuwata T. Effects of interferon on the human clonal cell line, RSa: inhibition of macromolecular synthesis. J Gen Virol. 1976 Oct;33(1):17–24. doi: 10.1099/0022-1317-33-1-17. [DOI] [PubMed] [Google Scholar]
  10. Fuse T. K., Morinaga N. Effects of interferon on cell and virus growth in transformed human cell lines. J Gen Virol. 1976 Oct;33(1):7–15. doi: 10.1099/0022-1317-33-1-7. [DOI] [PubMed] [Google Scholar]
  11. Garlick P. J., McNurlan M. A., Preedy V. R. A rapid and convenient technique for measuring the rate of protein synthesis in tissues by injection of [3H]phenylalanine. Biochem J. 1980 Nov 15;192(2):719–723. doi: 10.1042/bj1920719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gewert D. R., Moore G., Clemens M. J. Inhibition of cell division by interferons. The relationship between changes in utilization of thymidine for DNA synthesis and control of proliferation in Daudi cells. Biochem J. 1983 Sep 15;214(3):983–990. doi: 10.1042/bj2140983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gewert D. R., Moore G., Tilleray V. J., Clemens M. J. Inhibition of cell proliferation by interferons. 1. Effects on cell division and DNA synthesis in human lymphoblastoid (Daudi) cells. Eur J Biochem. 1984 Mar 15;139(3):619–625. doi: 10.1111/j.1432-1033.1984.tb08049.x. [DOI] [PubMed] [Google Scholar]
  14. Gewert D. R., Shah S., Clemens M. J. Inhibition of cell division by interferons: Changes in the transport and intracellular metabolism of thymidine in human lymphoblastoid (Daudi) cells. Eur J Biochem. 1981 Jun 1;116(3):487–492. doi: 10.1111/j.1432-1033.1981.tb05362.x. [DOI] [PubMed] [Google Scholar]
  15. Gunn J. M., Ballard F. J., Hanson R. W. Infulence of hormones and medium composition on the degradation of phosphoenolpyruvate carboxykinase (GTP) and total protein in Reuber H35 cells. J Biol Chem. 1976 Jun 25;251(12):3586–3593. [PubMed] [Google Scholar]
  16. Hammer J. A., 3rd, Rannels D. E. Protein turnover in pulmonary macrophages. Utilization of amino acids derived from protein degradation. Biochem J. 1981 Jul 15;198(1):53–65. doi: 10.1042/bj1980053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hershko A., Mamont P., Shields R., Tomkins G. M. "Pleiotypic response". Nat New Biol. 1971 Aug;232(33):206–211. [PubMed] [Google Scholar]
  18. Hildebran J. N., Airhart J., Stirewalt W. S., Low R. B. Prolyl-tRNA-based rates of protein and collagen synthesis in human lung fibroblasts. Biochem J. 1981 Aug 15;198(2):249–258. doi: 10.1042/bj1980249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnson T. C., Lerner M. P., Lancz G. J. Inhibition of protein synthesis in noninfected L cells by partially purified interferon preparations. J Cell Biol. 1968 Mar;36(3):617–624. doi: 10.1083/jcb.36.3.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jonak G. J., Knight E., Jr Selective reduction of c-myc mRNA in Daudi cells by human beta interferon. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1747–1750. doi: 10.1073/pnas.81.6.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kaminskas E. Serum-mediated stimulation of protein synthesis in Ehrlich ascites tumor cells. J Biol Chem. 1972 Sep 10;247(17):5470–5476. [PubMed] [Google Scholar]
  22. Lee G. T., Engelhardt D. L. Protein metabolism during growth of Vero Cells. J Cell Physiol. 1977 Aug;92(2):293–301. doi: 10.1002/jcp.1040920218. [DOI] [PubMed] [Google Scholar]
  23. Lengyel P. Biochemistry of interferons and their actions. Annu Rev Biochem. 1982;51:251–282. doi: 10.1146/annurev.bi.51.070182.001343. [DOI] [PubMed] [Google Scholar]
  24. Levy H. B., Merigan T. C. Interferon and uninfected cells. Proc Soc Exp Biol Med. 1966 Jan;121(1):53–55. doi: 10.3181/00379727-121-30695. [DOI] [PubMed] [Google Scholar]
  25. McKee E. E., Cheung J. Y., Rannels D. E., Morgan H. E. Measurement of the rate of protein synthesis and compartmentation of heart phenylalanine. J Biol Chem. 1978 Feb 25;253(4):1030–1040. [PubMed] [Google Scholar]
  26. Pain V. M., Henshaw E. C. Initiation of protein synthesis in Ehrlich ascites tumour cells. Evidence for physiological variation in the association of methionyl-tRNAf with native 40-S ribosomal subunits in vivo. Eur J Biochem. 1975 Sep 15;57(2):335–342. doi: 10.1111/j.1432-1033.1975.tb02306.x. [DOI] [PubMed] [Google Scholar]
  27. Pain V. M., Lewis J. A., Huvos P., Henshaw E. C., Clemens M. J. The effects of amino acid starvation on regulation of polypeptide chain initiation in Ehrlich ascites tumor cells. J Biol Chem. 1980 Feb 25;255(4):1486–1491. [PubMed] [Google Scholar]
  28. Sen G. C. Mechanism of interferon action: progress toward its understanding. Prog Nucleic Acid Res Mol Biol. 1982;27:105–156. doi: 10.1016/s0079-6603(08)60599-1. [DOI] [PubMed] [Google Scholar]
  29. Soeiro R., Amos H. Arrested protein synthesis in polysomes of cultured chick embryo cells. Science. 1966 Nov 4;154(3749):662–665. doi: 10.1126/science.154.3749.662. [DOI] [PubMed] [Google Scholar]
  30. Stirewalt W. S., Low R. B. Effects of insulin in vitro on protein turnover in rat epitrochlearis muscle. Biochem J. 1983 Feb 15;210(2):323–330. doi: 10.1042/bj2100323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tovey M., Brouty-Boyé D., Gresser I. Early effect of interferon on mouse leukemia cells cultivated in a chemostat. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2265–2269. doi: 10.1073/pnas.72.6.2265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. van Venrooij W. J., Henshaw E. C., Hirsch C. A. Effects of deprival of glucose or individual amino acids on polyribosome distribution and rate of protein synthesis in cultured mammalian cells. Biochim Biophys Acta. 1972 Jan 18;259(1):127–137. doi: 10.1016/0005-2787(72)90480-7. [DOI] [PubMed] [Google Scholar]

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