Inhibition of protein synthesis stimulates the transcription of human beta-interferon genes in Chinese hamster ovary cells.

Abstract

Using Chinese hamster ovary (CHO) cells transfected with a plasmid carrying the human .beta.-interferon gene, inhibitors of protein synthesis, in the absence of any other inducer, stimulate the production of interferon RNA; this effect is maintained in cells in which the plasmid sequences were amplified 25-50-fold. Nuclear transcription assays show that a major effect of cycloheximide is to increase the rate of transcription of the interferon gene. This contradicts the generally accepted explanation that inhibitors of protein synthesis augment interferon production by stabilizing interferon mRNA. The effects of double stranded RNA [poly(rI).cntdot.poly(rC)] on the induction of interferon RNA was studied in the presence and absence of cycloheximide. Poly(rI).cntdot.poly(rC) by itself may cause a transient increase in interferon RNA; however, in the presence of cycloheximide this effect is prolonged. An increase in transcription of the interferon gene(s) is not found as an early response to poly(rI).cntdot.poly(rC). Cells treated with cycloheximide or infected with Newcastle disease virus induce large amounts of a secreted 11-kDa [kilodalton] protein. This cellular protein is not inducible by poly(rI).cntdot.poly(rC). Both interferon and this 11-kDa protein may belong to a family of proteins in which production is regulated in a coordinate fashion during viral inhibition of cellular protein synthesis.