Specific inhibition of translocation by tubulosine in eukaryotic polysomes

The alkaloid tubulosine inhibits the process of peptide chain elongation by eukaryotic polysomes by specifically preventing the elongation-factor-2-dependent step of translocation. Tubulosine does not affect either the elongation-factor-1-dependent binding of aminoacyl-tRNA or peptide bond formation. The site of action of tubulosine appears to be independent from the ribosomal site involved in cycloheximide action, since the alkaloid is active in blocking polymerization and enzymic translocation by polysomes from a yeast mutant resistant to cycloheximide. Furthermore tubulosine does not affect the non-enzymic translocation which takes place in the presence of high potassium ion concentrations, whereas this reaction is strongly inhibited by cyclohemimede. The different steps of translocation are discussed to explain the reactions blocked by tubulosine and cycloheximide.