mTOR-independent translational control of the extrinsic cell death pathway by RalA.
Mol Cell Biol
; 26(20): 7345-57, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-16894031
ABSTRACT
Oncogenic potential is associated with translational regulation, and the prevailing view is that oncogenes use mTOR-dependent pathways to up-regulate the synthesis of proteins critical for transformation. In this study, we show that RalA, a key mediator of Ras transformation, is also linked to the translational machinery. At least part of this linkage, however, is independent of mTOR and acts through RalBP1 to suppress cdc42-mediated activation of S6 kinase and the translation of the antiapoptotic protein FLIP(S). This action, rather than contributing to transformation, opens a latent tumor-suppressive mechanism that can be activated by tumor necrosis factor-related apoptosis-inducing ligand. These results show that the translational machinery is linked to tumor suppression as well as cell-proliferative pathways and that the reestablishment of cell death pathways by activation of the Ral oncogenic program provides a means for selective therapeutic targeting of Ral-driven malignancies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Biossíntese de Proteínas
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Proteínas ral de Ligação ao GTP
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article