The putative role of inhibition of protein synthesis within the antiproliferative effect of interferon was analyzed in serum-stimulated Swiss 3T3 mouse fibroblasts. We observed an apparent coupling between protein-synthesis inhibition during G1 and a delayed entry into the S-phase. To reveal any specificity in the protein-synthesis inhibition, we measured the amounts of synthesis of 56 major individual proteins, by using isotope double-labelling and two-dimensional gel electrophoresis. Interferon inhibited preferentially the synthesis of proteins which were increased after serum stimulation, whereas proteins synthesized in constant or decreased amounts after serum stimulation were significantly more resistant. The effects of interferon were also compared to those of 5,6-dichloro-1-beta-ribofuranosylbenzimidazole (DRB), an inhibitor of transcription. All interferon-sensitive proteins studied were inhibited by DRB treatment, but in addition DRB also inhibited several proteins which were completely resistant to interferon. We conclude that interferon primarily inhibits protein synthesis originating from a subset of newly transcribed messenger RNAs. The mechanism(s) for inhibition of protein synthesis and the possible relationship to the antiproliferative and antiviral effects of interferon are discussed.
Animals Blood