Radicicol induces intracellular accumulation of glycan-deficient clusterin variant.
Biochem Biophys Res Commun
; 458(3): 555-560, 2015 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-25680466
ABSTRACT
Proteostasis regulation using naturally occurring small molecules has been considered as a promising strategy for manipulating cancer sensitivity and therapy. Here, we identify a small molecule Hsp90 inhibitor radicicol that induces intracellular accumulation of cytotoxic clusterin variant. In the mechanistic basis, this variant proved to be a product disposed from the stressed ER. During this process, inhibitory effect of radicicol on protein degradation results in cytosolic accumulation of glycan-deficient clusterin variant that signals cell death. These results provide a therapeutic insight into the targeted proteostasis perturbation of clusterin as an anti-cancer strategy.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Síntese de Proteínas
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Proteínas de Choque Térmico HSP90
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Macrolídeos
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Clusterina
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article