TY - JOUR
T1 - Mechanism of action of the 12,13-epoxytrichothecene, anguidine, an inhibitor of protein synthesis
AU - Liao, Lon Lon
AU - Grollman, Arthur P.
AU - Horwitz, Susan B.
N1 - Funding Information:
This work was supported by Division of Cancer Treatment contract N01-CM-43787 and Public Health Service grant CA 15714 from the National Cancer Institute, National Institutes of Health, Department of Health, Education and Welfare. S.B.H. is a recipient of an Irma T. Hirschl Career Scientist Award.
PY - 1976/12/1
Y1 - 1976/12/1
N2 - 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.
AB - 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.
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U2 - 10.1016/0005-2787(76)90230-6
DO - 10.1016/0005-2787(76)90230-6
M3 - Article
C2 - 999905
AN - SCOPUS:0017193506
SN - 0005-2787
VL - 454
SP - 273
EP - 284
JO - BBA Section Nucleic Acids And Protein Synthesis
JF - BBA Section Nucleic Acids And Protein Synthesis
IS - 2
ER -