p53/TAp63 and AKT regulate mammalian target of rapamycin complex 1 (mTORC1) signaling through two independent parallel pathways in the presence of DNA damage.
J Biol Chem
; 289(7): 4083-94, 2014 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-24366874
ABSTRACT
Under conditions of DNA damage, the mammalian target of rapamycin complex 1 (mTORC1) is inhibited, preventing cell cycle progression and conserving cellular energy by suppressing translation. We show that suppression of mTORC1 signaling to 4E-BP1 requires the coordinated activity of two tumor suppressors, p53 and p63. In contrast, suppression of S6K1 and ribosomal protein S6 phosphorylation by DNA damage is Akt-dependent. We find that loss of either p53, required for the induction of Sestrin 1/2, or p63, required for the induction of REDD1 and activation of the tuberous sclerosis complex, prevents the DNA damage-induced suppression of mTORC1 signaling. These data indicate that the negative regulation of cap-dependent translation by mTORC1 inhibition subsequent to DNA damage is abrogated in most human cancers.
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MEDLINE
Assunto principal:
Fatores de Transcrição
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Dano ao DNA
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Transdução de Sinais
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Proteína Supressora de Tumor p53
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Proteínas Supressoras de Tumor
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Complexos Multiproteicos
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Proteínas Proto-Oncogênicas c-akt
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Serina-Treonina Quinases TOR
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Neoplasias
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article