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1.
Cell Death Differ ; 27(5): 1744, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31641239

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Cell Death Differ ; 25(10): 1766-1780, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29523872

RESUMO

Stress granules are cytoplasmic mRNA-protein complexes that form upon the inhibition of translation initiation and promote cell survival in response to environmental insults. However, they are often associated with pathologies, including neurodegeneration and cancer, and changes in their dynamics are implicated in ageing. Here we show that the mTOR effector kinases S6 kinase 1 (S6K1) and S6 kinase 2 (S6K2) localise to stress granules in human cells and are required for their assembly and maintenance after mild oxidative stress. The roles of S6K1 and S6K2 are distinct, with S6K1 having a more significant role in the formation of stress granules via the regulation of eIF2α phosphorylation, while S6K2 is important for their persistence. In C. elegans, the S6 kinase orthologue RSKS-1 promotes the assembly of stress granules and its loss of function sensitises the nematodes to stress-induced death. This study identifies S6 kinases as regulators of stress granule dynamics and provides a novel link between mTOR signalling, translation inhibition and survival.


Assuntos
Grânulos Citoplasmáticos/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Arsenitos/toxicidade , Caenorhabditis elegans/metabolismo , DNA Helicases/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Células HeLa , Humanos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/metabolismo , Interferência de RNA , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , RNA Interferente Pequeno/metabolismo , Proteína Regulatória Associada a mTOR/antagonistas & inibidores , Proteína Regulatória Associada a mTOR/genética , Proteína Regulatória Associada a mTOR/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/antagonistas & inibidores , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Transdução de Sinais/efeitos dos fármacos
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