Human Interferon γ Potently Induces the Synthesis of a 55-kDa Protein (γ2) Highly Homologous to Rabbit Peptide Chain Release Factor and Bovine Tryptophanyl-tRNA Synthetase

An interferon γ (IFN-γ)-inducible protein, γ2, 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 γ2 protein is found to be highly induced by IFN-γ, whereas no induction was seen after addition of IFN-α to AMA cells. A γ2-specific 2.7-kilobase mRNA was likewise seen to accumulate selectively in response to IFN-γ in these cells. Comparison of the predicted amino acid sequence of γ2 to proteins in GenBank data bases revealed that γ2 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 γ2 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 γ2 protein is shown to possess tryptophan-dependentaminoacyl-tRNA synthetase activity and thus constitutes an enzymatic activity involved in the biological activity of IFN-γ.