P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP.
Cell Death Dis
; 5: e1131, 2014 Mar 20.
Article
em En
| MEDLINE
| ID: mdl-24651434
ABSTRACT
The short isoform of ErbB3-binding protein 1 (Ebp1), p42, is considered to be a potent tumor suppressor in a number of human cancers, although the mechanism by which it exerts this tumor-suppressive activity is unclear. Here, we report that p42 interacts with the cSH2 domain of the p85 subunit of phosphathidyl inositol 3-kinase (PI3K), leading to inhibition of its lipid kinase activity. Importantly, we found that p42 induces protein degradation of the p85 subunit and further identified HSP70/CHIP complex as a novel E3 ligase for p85 that is responsible for p85 ubiquitination and degradation. In this process, p42 couples p85 to the HSP70/CHIP-mediated ubiquitin-proteasomal system (UPS), thereby promoting a reduction of p85 levels both in vitro and in vivo. Thus, the tumor-suppressing effects of p42 in cancer cells are driven by negative regulation of the p85 subunit of PI3K.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Proteínas Nucleares
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Proteínas de Ligação a RNA
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Proteínas de Choque Térmico HSP70
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Ubiquitina-Proteína Ligases
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Complexo de Endopeptidases do Proteassoma
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Proteínas Adaptadoras de Transdução de Sinal
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Classe Ia de Fosfatidilinositol 3-Quinase
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Glioma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2014
Tipo de documento:
Article