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  • 标题:Mechanism of Action of the Mycotoxin Trichodermin, a 12,13-Epoxytrichothecene
  • 本地全文:下载
  • 作者:Cha-mer Wei ; Bent S. Hansen ; Maurice H. Vaughan
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1974
  • 卷号:71
  • 期号:3
  • 页码:713-717
  • DOI:10.1073/pnas.71.3.713
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Trichodermin is a member of a group of closely related compounds--the 12,13-epoxytrichothecenes--that form a medically and economically important class of mycotoxins produced by fungi that spoil fruit and grain. Our studies show that trichodermin is a very potent inhibitor of protein synthesis in mammalian cells. Since ribosomes remain in polyribosomes in inhibited cells, trichodermin inhibits the elongation and/or termination processes of protein synthesis. In vitro, trichodermin is a potent inhibitor of the peptidyl transferase activity required for elongation and/or termination. An in vitro comparison of the effects of three peptidyl transferase inhibitors on elongation and termination indicates that anisomycin acts primarily on elongation while trichodermin and sparsomycin act primarily on termination. A new in vivo test to distinguish elongation inhibitors from termination inhibitors confirms that trichodermin inhibits primarily the termination process. Thus trichodermin inhibits protein synthesis by blocking the activity of peptidyl transferase required for termination. These studies suggest that the toxicosis caused by one of the 12,13-epoxytrichothecenes is due to its action as a protein synthesis inhibitor involving the peptidyl transferase activity of the eukaryotic ribosomes.
  • 关键词:human cells ; protein synthesis ; release factor ; peptidyl transferase ; antitumor
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