Specific Inhibition of Translocation by Tubulosine in Eukaryotic Polysomes

Abstract

The alkaloid tubulosine [from bark extracts of Pogonopus tubulosis] 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 [Saccharomyces cerevisiae] resistant to cycloheximide. 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 cycloheximide. The different steps of translocation are discussed to explain the reactions blocked by tubulosine and cycloheximide.