Mechanism of action of the 12,13-epoxytrichothecene, anguidine, an inhibitor of protein synthesis

Lon Lon Liao, Arthur P. Grollman, Susan B. Horwitz

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Abstract

Anguidine, muconomycin A, T-2 toxin, crotocin and trichodermin, a group of 12,13-epoxytrichothecenes, inhibit protein synthesis in HeLa cells and in rabbit reticulocyte lysates. These five mycotoxins can be divided into two groups on the basis of the reversibility of their effects in HeLa cells, and kinetics of inhibition and effects on polyribosome structure in rabbit reticulocyte lysates. Anguidine, muconomycin A and T-2 toxin are irreversible inhibitors of protein synthesis; crotocin and trichodermin are reversible inhibitors of protein synthesis. After addition of low concentrations (1 μM) of anguidine, muconomycin A or T-2 toxin to rabbit reticulocyte lysates, polyribosomes are broken down to monosomes. At higher concentrations, 1 mM, these drugs begin to freeze the polyribosomes. Crotocin and trichodermin freeze the polyribosomes at a concentration of 10 μM. We conclude that anguidine, muconomycin A and T-2 toxin act primarily as inhibitors of initiation of protein synthesis, whereas crotocin and trichodermin inhibit the process of chain elongation.

Original languageEnglish (US)
Pages (from-to)273-284
Number of pages12
JournalBBA Section Nucleic Acids And Protein Synthesis
Volume454
Issue number2
DOIs
Publication statusPublished - Dec 1 1976

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ASJC Scopus subject areas

  • Medicine(all)

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