mTORC1 induces eukaryotic translation initiation factor 4E interaction with TOS-S6 kinase 1 and its activation.
Cell Cycle
; 20(9): 839-854, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33938392
ABSTRACT
Eukaryotic translation initiation factor 4E was recently shown to be a substrate of mTORC1, suggesting it may be a mediator of mTORC1 signaling. Here, we present evidence that eIF4E phosphorylated at S209 interacts with TOS motif of S6 Kinase1 (S6K1). We also show that this interaction is sufficient to overcome rapamycin sensitivity and mTORC1 dependence of S6K1. Furthermore, we show that eIF4E-TOS interaction relieves S6K1 from auto-inhibition due to carboxy terminal domain (CTD) and primes it for hydrophobic motif (HM) phosphorylation and activation in mTORC1 independent manner. We conclude that the role of mTORC1 is restricted to engaging eIF4E with S6K1-TOS motif to influence its state of HM phosphorylation and inducing its activation.
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MEDLINE
Assunto principal:
Proteínas Quinases S6 Ribossômicas
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Fator de Iniciação 4E em Eucariotos
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Alvo Mecanístico do Complexo 1 de Rapamicina
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article