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. 1991 Dec 15;88(24):11520–11524. doi: 10.1073/pnas.88.24.11520

Human interferon gamma potently induces the synthesis of a 55-kDa protein (gamma 2) highly homologous to rabbit peptide chain release factor and bovine tryptophanyl-tRNA synthetase.

J Fleckner 1, H H Rasmussen 1, J Justesen 1
PMCID: PMC53167  PMID: 1763065

Abstract

An interferon gamma (IFN-gamma)-inducible protein, gamma 2, was identified by two-dimensional gel electrophoresis of transformed human amnion (AMA) cell proteins. cDNA clones coding for this protein have been isolated and characterized as encoding a polypeptide with a predicted molecular weight of 53,165 and a pI of 6.16. Both values are in good agreement with those observed in two-dimensional gel electrophoresis. The gamma 2 protein is found to be highly induced by IFN-gamma, whereas no induction was seen after addition of IFN-alpha to AMA cells. A gamma 2-specific 2.7-kilobase mRNA was likewise seen to accumulate selectively in response to IFN-gamma in these cells. Comparison of the predicted amino acid sequence of gamma 2 to proteins in GenBank data bases revealed that gamma 2 is highly homologous to rabbit peptide chain release factor [Lee, C. C., Craigen, W. J., Muzny, D. M., Harlow, E. & Caskey, C. T. (1990) Proc. Natl. Acad. Sci. USA 87, 3508-3512] and bovine tryptophanyl-tRNA synthetase [M. Garret, V. Trezeguet, B. Pajot, J. C. Gandar, M. Merle, M. Guegiev, J. P. Benedetto, C. Sarger, J. Alteriot, J. La Bouessec, J. Labouesse, and J. Bonnet (1990), GenBank accession no. X52113]. Amino acid sequence similarities of 94% and 97%, respectively, are found, which in general would indicate that gamma 2 represents the human equivalent to either of these two mammalian genes. Based on these sequence similarities, the current data raise the possibility that tryptophanyl-tRNA charging and peptide chain release are carried out by the same enzyme. The gamma 2 protein is shown to possess tryptophan-dependent aminoacyl-tRNA synthetase activity and thus constitutes an enzymatic activity involved in the biological activity of IFN-gamma.

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Selected References

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

  1. Amaldi I., Reith W., Berte C., Mach B. Induction of HLA class II genes by IFN-gamma is transcriptional and requires a trans-acting protein. J Immunol. 1989 Feb 1;142(3):999–1004. [PubMed] [Google Scholar]
  2. Cashel M., Lazzarini R. A., Kalbacher B. An improved method for thin-layer chromatography of nucleotide mixtures containing 32P-labelled orthophosphate. J Chromatogr. 1969 Mar 11;40(1):103–109. doi: 10.1016/s0021-9673(01)96624-5. [DOI] [PubMed] [Google Scholar]
  3. Celis J. E., Gesser B., Rasmussen H. H., Madsen P., Leffers H., Dejgaard K., Honore B., Olsen E., Ratz G., Lauridsen J. B. Comprehensive two-dimensional gel protein databases offer a global approach to the analysis of human cells: the transformed amnion cells (AMA) master database and its link to genome DNA sequence data. Electrophoresis. 1990 Dec;11(12):989–1071. doi: 10.1002/elps.1150111202. [DOI] [PubMed] [Google Scholar]
  4. Celis J. E., Justesen J., Madsen P. S., Lovmand J., Pedersen Ratz G., Celis A. Major proteins induced and down-regulated by interferons in human cultured cells: identification of a unique set of proteins induced by interferon-alpha in epithelial, fibroblast, and lymphoid cells. Leukemia. 1987 Dec;1(12):800–813. [PubMed] [Google Scholar]
  5. 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]
  6. Dai W., Gupta S. L. Regulation of indoleamine 2,3-dioxygenase gene expression in human fibroblasts by interferon-gamma. Upstream control region discriminates between interferon-gamma and interferon-alpha. J Biol Chem. 1990 Nov 15;265(32):19871–19877. [PubMed] [Google Scholar]
  7. De Benedetti A., Baglioni C. Inhibition of mRNA binding to ribosomes by localized activation of dsRNA-dependent protein kinase. Nature. 1984 Sep 6;311(5981):79–81. doi: 10.1038/311079a0. [DOI] [PubMed] [Google Scholar]
  8. Eriani G., Delarue M., Poch O., Gangloff J., Moras D. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature. 1990 Sep 13;347(6289):203–206. doi: 10.1038/347203a0. [DOI] [PubMed] [Google Scholar]
  9. Fan X. D., Stark G. R., Bloom B. R. Molecular cloning of a gene selectively induced by gamma interferon from human macrophage cell line U937. Mol Cell Biol. 1989 May;9(5):1922–1928. doi: 10.1128/mcb.9.5.1922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Farber J. M. A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5238–5242. doi: 10.1073/pnas.87.14.5238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  12. Feng G. S., Taylor M. W. Interferon gamma-resistant mutants are defective in the induction of indoleamine 2,3-dioxygenase. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7144–7148. doi: 10.1073/pnas.86.18.7144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fling S. P., Gregerson D. S. Peptide and protein molecular weight determination by electrophoresis using a high-molarity tris buffer system without urea. Anal Biochem. 1986 May 15;155(1):83–88. doi: 10.1016/0003-2697(86)90228-9. [DOI] [PubMed] [Google Scholar]
  14. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gubler U. A one tube reaction for the synthesis of blunt-ended double-stranded cDNA. Nucleic Acids Res. 1988 Mar 25;16(6):2726–2726. doi: 10.1093/nar/16.6.2726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guyre P. M., Morganelli P. M., Miller R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest. 1983 Jul;72(1):393–397. doi: 10.1172/JCI110980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ijzermans J. N., Marquet R. L. Interferon-gamma: a review. Immunobiology. 1989 Oct;179(4-5):456–473. doi: 10.1016/S0171-2985(89)80049-X. [DOI] [PubMed] [Google Scholar]
  18. Interferon nomenclature. Nature. 1980 Jul 10;286(5769):110–110. doi: 10.1038/286110a0. [DOI] [PubMed] [Google Scholar]
  19. Kisselev L. L., Favorova O. O., Kovaleva G. K. Tryptophanyl-tRNA synthetase from beef pancreas. Methods Enzymol. 1979;59:234–257. doi: 10.1016/0076-6879(79)59087-9. [DOI] [PubMed] [Google Scholar]
  20. Lee C. C., Craigen W. J., Muzny D. M., Harlow E., Caskey C. T. Cloning and expression of a mammalian peptide chain release factor with sequence similarity to tryptophanyl-tRNA synthetases. Proc Natl Acad Sci U S A. 1990 May;87(9):3508–3512. doi: 10.1073/pnas.87.9.3508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Leffers H., Gropp F., Lottspeich F., Zillig W., Garrett R. A. Sequence, organization, transcription and evolution of RNA polymerase subunit genes from the archaebacterial extreme halophiles Halobacterium halobium and Halococcus morrhuae. J Mol Biol. 1989 Mar 5;206(1):1–17. doi: 10.1016/0022-2836(89)90519-6. [DOI] [PubMed] [Google Scholar]
  22. Lemaire G., Gros C., Epely S., Kaminski M., Labouesse B. Multiple forms of tryptophanyl-tRNA synthetase from beef pancreas. Eur J Biochem. 1975 Feb 3;51(1):237–252. doi: 10.1111/j.1432-1033.1975.tb03924.x. [DOI] [PubMed] [Google Scholar]
  23. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  24. Luster A. D., Unkeless J. C., Ravetch J. V. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985 Jun 20;315(6021):672–676. doi: 10.1038/315672a0. [DOI] [PubMed] [Google Scholar]
  25. Luster A. D., Weinshank R. L., Feinman R., Ravetch J. V. Molecular and biochemical characterization of a novel gamma-interferon-inducible protein. J Biol Chem. 1988 Aug 25;263(24):12036–12043. [PubMed] [Google Scholar]
  26. Newburger P. E., Ezekowitz R. A., Whitney C., Wright J., Orkin S. H. Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5215–5219. doi: 10.1073/pnas.85.14.5215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ozaki Y., Edelstein M. P., Duch D. S. Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1242–1246. doi: 10.1073/pnas.85.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pestka S., Langer J. A., Zoon K. C., Samuel C. E. Interferons and their actions. Annu Rev Biochem. 1987;56:727–777. doi: 10.1146/annurev.bi.56.070187.003455. [DOI] [PubMed] [Google Scholar]
  29. Wallach D., Fellous M., Revel M. Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature. 1982 Oct 28;299(5886):833–836. doi: 10.1038/299833a0. [DOI] [PubMed] [Google Scholar]
  30. Webster T., Tsai H., Kula M., Mackie G. A., Schimmel P. Specific sequence homology and three-dimensional structure of an aminoacyl transfer RNA synthetase. Science. 1984 Dec 14;226(4680):1315–1317. doi: 10.1126/science.6390679. [DOI] [PubMed] [Google Scholar]
  31. Weil J., Epstein C. J., Epstein L. B., Sedmak J. J., Sabran J. L., Grossberg S. E. A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons. Nature. 1983 Feb 3;301(5899):437–439. doi: 10.1038/301437a0. [DOI] [PubMed] [Google Scholar]
  32. Werner E. R., Werner-Felmayer G., Fuchs D., Hausen A., Reibnegger G., Wachter H. Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2,3-dioxygenase activity in human cells and cell lines by interferon-gamma. Biochem J. 1989 Sep 15;262(3):861–866. doi: 10.1042/bj2620861. [DOI] [PMC free article] [PubMed] [Google Scholar]

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