Initiation and elongation of protein synthesis in growing cells: Differential inhibition by cycloheximide and emetine

Abstract

The mechanisms of action of cycloheximide and emetine in exponentially growing Chinese hamster ovary cells have been studied (a) by measuring the incorporation of [ 35S]methionine into N-terminal and internal positions of nascent peptide chains by an Edman degradation modified for handling a large number of samples and (b) by determining the size distribution of polysomes in the presence of the drugs. These combined techniques have confirmed that all three phases of protein synthesis (initiation, elongation, and termination) are susceptible to inhibition by cycloheximide and have shown that the primary sensitive step varies with the concentration of drug between 10 −9 and 10 −3 m. At the lowest doses, initiation appears, by these criteria, to be the step most sensitive to inhibition by cycloheximide, while emetine seems to act primarily on elongation.