The marine polyketide myriaporone 3/4 stalls translation by targeting the elongation phase.
Chembiochem
; 14(2): 260-4, 2013 Jan 21.
Article
em En
| MEDLINE
| ID: mdl-23303710
ABSTRACT
Myriaporone 3/4, a cytotoxic polyketide, has been reported as an inhibitor of eukaryotic protein synthesis. However, the mechanism by which it inhibits translation was unknown. Here we show that myriaporone 3/4 stalls protein synthesis in the elongation phase by inducing phosphorylation of eukaryotic elongation factor 2. The phosphorylation results from direct binding of myriaporone 3/4 to eukaryotic elongation factor 2 kinase. Our study also shows that myriaporone 3/4 in the nanomolar range inhibits in vitro tube formation by endothelial cells without being cytotoxic. In general, myriaporone 3/4 was at least 300 times less toxic to primary cells than to tumor cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piranos
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Biossíntese de Proteínas
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Fator 2 de Elongação de Peptídeos
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Inibidores da Angiogênese
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Compostos de Epóxi
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Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article