GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress.
Int J Mol Med
; 19(3): 475-83, 2007 Mar.
Article
em En
| MEDLINE
| ID: mdl-17273797
ABSTRACT
Cells regulate the rate of protein synthesis during conditions of cell stress to adapt to environmental changes. However, the molecular interactions between signaling pathways controlling translation and the cellular response to stress remain to be elucidated. Here, we show that the expression of growth arrest and DNA damage protein 34 (GADD34) is induced by energy depletion and that the expression of this protein protects cells from apoptotic cell death. During conditions of cell stress, GADD34 forms a stable complex with tuberous sclerosis complex (TSC) 1/2, causes TSC2 dephosphorylation, and inhibits signaling by mammalian target of the rapamycin (mTOR). These findings demonstrate that crosstalk between GADD34 and the mTOR signaling pathways contributes to the response of the protein synthetic machinery to environmental stress. GADD34 may find clinical potential as a target drug for the treatment of mTOR-associated diseases.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Transdução de Sinais
/
Antígenos de Diferenciação
/
Proteínas de Ciclo Celular
/
Proteínas Supressoras de Tumor
/
Metabolismo Energético
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão