Investigation of the mechanism of action of a potent pateamine A analog, des-methyl, des-amino pateamine A (DMDAPatA).
Biochem Cell Biol
; 98(4): 502-510, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32008367
ABSTRACT
The natural product pateamineA (PatA) is a highly potent antiproliferative agent. PatA and the simplified analog desmethyl, desamino pateamineA (DMDAPatA) have exhibited cytotoxicity selective for rapidly proliferating cells, and have been shown to inhibit cap-dependent translation initiation through binding to eIF4A (eukaryotic initiation factor 4A) of the eIF4F complex. PatA and DMDAPatA are both known to stimulate the RNA-dependent ATPase, and ATP-dependent RNA helicase activities of eIF4A. The impact of other eIF4F components, eIF4E and eIF4G, on DMDAPatA action were investigated in vitro and in cultured mammalian cells. The perturbation of the eIF4A-eIF4G association was found to be eIF4E- and mRNA cap-dependent. An inhibitory effect on helicase activity of eIF4A was observed when it was part of a complex that mimicked the eIF4F complex. We propose a model of action for DMDAPatA (and by supposition PatA) where the cellular activity of the compound is dependent on an "active" eIF4F complex.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
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RNA Mensageiro
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Adenosina Trifosfatases
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Macrolídeos
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Fator de Iniciação 4A em Eucariotos
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Compostos de Epóxi
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos