Studies will be undertaken to gain further insight into the mechanism of action of the interferons (IFNs). Proposed studies will characterize the antiviral and antiproliferative phenotypes of cells which, as a result of transfection, produce the IFN-induced gp96, 67kD, 56kD, or 42kD proteins. In addition, the cDNAs encoding these proteins will be used to: 1) study the genes encoding these proteins; 2) characterize the promoters responsible for their responsiveness to the IFNs; and 3) determine the chromosomal localization of each gene. Characterization of the IFN-induced 56,000 dalton protein has resulted in the demonstration that this protein is a tryptophanyl tRNA synthetase. Studies proposed will evaluate the relatedness of this protein to the mammalian peptide chain release factor and the role this protein plays in the biological actions of the IFNs. The characterizations of genes and their products that are up-regulated in response to the IFNs are being undertaken to provide insight into the mechanisms by which the IFNs mediate their effects and to enable the development of a methodology by which the responsiveness of tumor tissues to the anticellular effects of the IFNs can be established in vitro prior to their use as therapeutic agents.