Hsp70 and Hsp90 oppositely regulate TGF-ß signaling through CHIP/Stub1.
Biochem Biophys Res Commun
; 446(1): 387-92, 2014 Mar 28.
Article
em En
| MEDLINE
| ID: mdl-24613385
ABSTRACT
Transforming growth factor-ß (TGF-ß) signaling plays an important role in regulation of a wide variety of cellular processes. Canonical TGF-ß signaling is mediated by Smads which were further regulated by several factors. We previously reported that E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein, also named Stub1) controlled the sensitivity of TGF-ß signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation. Here, we present evidence that Hsp70 and Hsp90 regulate the complex formation of Smad3/CHIP. Furthermore, we observed that over-expressed Hsp70 or inhibition of Hsp90 by geldanamycin (GA) leads to facilitated CHIP-induced ubiquitination and degradation of Smad3, which finally enhances TGF-ß signaling. In contrast, over-expressed Hsp90 antagonizes CHIP mediated Smad3 ubiquitination and degradation and desensitizes cells in response to TGF-ß signaling. Taken together, our data reveal an opposite role of Hsp70 and Hsp90 in regulating TGF-ß signaling by implicating CHIP-mediated Smad3 ubiquitination and degradation. This study provides a new insight into understanding the regulation of the TGF-ß signaling by chaperones.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
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Proteínas de Choque Térmico HSP90
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Proteínas de Choque Térmico HSP70
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Ubiquitina-Proteína Ligases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China