Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation.
Science
; 338(6109): 956-9, 2012 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-23112296
ABSTRACT
Aberrant signaling through the class I phosphatidylinositol 3-kinase (PI3K)-Akt axis is frequent in human cancer. Here, we show that Beclin 1, an essential autophagy and tumor suppressor protein, is a target of the protein kinase Akt. Expression of a Beclin 1 mutant resistant to Akt-mediated phosphorylation increased autophagy, reduced anchorage-independent growth, and inhibited Akt-driven tumorigenesis. Akt-mediated phosphorylation of Beclin 1 enhanced its interactions with 14-3-3 and vimentin intermediate filament proteins, and vimentin depletion increased autophagy and inhibited Akt-driven transformation. Thus, Akt-mediated phosphorylation of Beclin 1 functions in autophagy inhibition, oncogenesis, and the formation of an autophagy-inhibitory Beclin 1/14-3-3/vimentin intermediate filament complex. These findings have broad implications for understanding the role of Akt signaling and intermediate filament proteins in autophagy and cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Transformação Celular Neoplásica
/
Proteínas Proto-Oncogênicas c-akt
/
Proteínas Reguladoras de Apoptose
/
Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article