Mechanism of Action of the Mycotoxin Trichodermin, a 12,13-Epoxytrichothecene

Wei, Cha-Mer; Hansen, Bent S.; Vaughan, Maurice H.; McLaughlin, Calvin S.

doi:10.1073/pnas.71.3.713

Cited by 53 publications

(21 citation statements)

References 19 publications

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“…They suggested that in yeast trichodermin acts as an inhibitor of termination. In addition, Wei et al (33) have reported trichodermin to be a preferential inhibitor of termination in intact HeLa cells. Their data ( Table 2 in reference 33), like ours (Fig.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Protein Synthesis in Intact HeLa Cells

Tscherne

Pestka

1975

Antimicrob Agents Chemother

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Polysome analysis has proved to be a sensitive probe for the mode of action of inhibitors of protein synthesis in intact HeLa cells. To classify the active compounds as inhibitors of initiation, elongation, or termination, their effects on the cellular polyribosome pattern were compared under three conditions. These conditions tested (i) their direct effect on the polyribosome profile; (ii) their effect on ribosome run-off produced by hypertonicity; and (iii) their effects on recovery from hypertonicity. Using this technique, diacetoxyscirpenol, 2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamide, and three alkaloids, harringtonine, isoharringtonine, and homoharringtonine, were found to be inhibitors of initiation. Polysome analysis indicated that in HeLa cells 7.8 x 10-7 M pactamycin, which inhibited protein synthesis 94%, interfered with elongation as well as initiation under these conditions. Emetine, anisomycin, cycloheximide, and trichodermin each gave polysome patterns consistent with inhibition of elongation. Fusidic acid and aurintricarboxylic acid inhibited incorporation of ["CC]

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Section: Resultsmentioning

confidence: 99%

Inhibition of Protein Synthesis in Intact HeLa Cells

Tscherne

Pestka

1975

Antimicrob Agents Chemother

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“…However, trichodermin has been shown to have inhibitory effects on plant growth including wheat coleoptiles ( Triticum aestivum ), tobacco ( Nicotiana tabacum ), beans ( Phaseolus vulgaris ), and corn ( Zea mays ) (Cutler and LeFiles, 1978). Mechanistically, trichodermin has been shown to be a very potent inhibitor of eukaryotic protein synthesis, specifically by inhibiting peptide-bond formation at the initiation stage of translation (Carter et al, 1976) and by inhibiting peptidyl transferase activity required for translational elongation and/or termination (Wei et al, 1974). …”

Section: Terpenoid Compoundsmentioning

confidence: 99%

The Diversity of Anti-Microbial Secondary Metabolites Produced by Fungal Endophytes: An Interdisciplinary Perspective

Mousa¹,

Raizada²

2013

Front. Microbiol.

237

121

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Endophytes are microbes that inhabit host plants without causing disease and are reported to be reservoirs of metabolites that combat microbes and other pathogens. Here we review diverse classes of secondary metabolites, focusing on anti-microbial compounds, synthesized by fungal endophytes including terpenoids, alkaloids, phenylpropanoids, aliphatic compounds, polyketides, and peptides from the interdisciplinary perspectives of biochemistry, genetics, fungal biology, host plant biology, human and plant pathology. Several trends were apparent. First, host plants are often investigated for endophytes when there is prior indigenous knowledge concerning human medicinal uses (e.g., Chinese herbs). However, within their native ecosystems, and where investigated, endophytes were shown to produce compounds that target pathogens of the host plant. In a few examples, both fungal endophytes and their hosts were reported to produce the same compounds. Terpenoids and polyketides are the most purified anti-microbial secondary metabolites from endophytes, while flavonoids and lignans are rare. Examples are provided where fungal genes encoding anti-microbial compounds are clustered on chromosomes. As different genera of fungi can produce the same metabolite, genetic clustering may facilitate sharing of anti-microbial secondary metabolites between fungi. We discuss gaps in the literature and how more interdisciplinary research may lead to new opportunities to develop bio-based commercial products to combat global crop and human pathogens.

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“…1A was estimated to be about 30% by densitometry of the cell-free translation products, and therefore purification to homogeneity required a 2000-to 3000-fold purification from total mRNA (750/ 0.3). These polysomes were prepared in the continuous presence of trichodermin at 1 ,ug/ml [a fungal antibiotic that is thought to inhibit termination of translation (35,36)]. It is believed that polysomes prepared in the presence of trichodermin might have longer nascent chains (and therefore more and greater exposure of antigenic sites per polysome) than polysomes isolated in the presence of chain-elongation inhibitors such as cycloheximide.…”

Section: Resultsmentioning

confidence: 99%

cDNA clones for the heavy chain of HLA-DR antigens obtained after immunopurification of polysomes by monoclonal antibody.

Korman¹,

Knudsen²,

Kaufman³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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A monoclonal antibody (HC 2. 1) directed against the separated heavy chain of HLA-DR has been prepared. By binding HC 2.1 to polysomes from human B lymphoblastoid cells followed by the use of a protein A-Sepharose column as an immunoadsorbent, we have purified the mRNA coding for the HLA-DR heavy chain nearly to homogeneity. The immunopurified mRNA has been used to prepare labeled cDNA with which to probe cDNA libraries. Double-stranded cDNA was also made from the immunopurified mRNA and cloned directly into pBR322. Two clones, one from each of the above procedures, positively selected DR heavy chain message as assayed by cell-free translation and immunoprecipitation. One clone, pDRH-2 [500 base pairs plus 75 base pairs of poly(A)] contains the entire 3' untranslated region as well as coding information for the carboxy-terminal hydrophilic intracellular domain and part of the hydrophobic transmembrane region. Results of carboxypeptidase digestion of the heavy chains from detergent-solubilized (p34) and papaintreated (p33) HLA-DR antigen were consistent with the predicted protein sequence. Specific immunopurification of polysomes by defined monoclonal antibodies followed by direct cloning ofcDNA to the highly purified mRNA is a powerful method for obtaining identified cDNA clones.

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Mechanism of Action of the Mycotoxin Trichodermin, a 12,13-Epoxytrichothecene

Cited by 53 publications

References 19 publications

Inhibition of Protein Synthesis in Intact HeLa Cells

Inhibition of Protein Synthesis in Intact HeLa Cells

The Diversity of Anti-Microbial Secondary Metabolites Produced by Fungal Endophytes: An Interdisciplinary Perspective

cDNA clones for the heavy chain of HLA-DR antigens obtained after immunopurification of polysomes by monoclonal antibody.

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