Journal Article

The mTOR-S6 kinase pathway promotes stress granule assembly

Abou-Hamdan, Hussein, Sfakianos, Aristeidis P., Pang, Yoke Fei, Ashe, Mark P., Désaubry, Laurent, Poulin, Gino B., Kritsiligkou, Paraskevi, Needs, Hope, Mellor, Laura E., Whitmarsh, Alan J.

2018

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/106 / 13/89 / 13/95 / 14 / 631/208 / 631/80 / 64/11 / 82/51 / Aging / Animals / Apoptosis / Arsenites - toxicity / Biochemistry / Biomedical and Life Sciences / Caenorhabditis elegans - metabolism / Cancer / Cell Biology / Cell Cycle Analysis / Cell survival / Cellular Biology / Cytoplasmic Granules - metabolism / DNA Helicases - metabolism / Eukaryotic Initiation Factor-2 - metabolism / Granule cells / HeLa Cells / Humans / Life Sciences / mRNA / Neurodegeneration / Oxidative stress / Oxidative Stress - drug effects / Phosphorylation / Phosphorylation - drug effects / Poly-ADP-Ribose Binding Proteins - metabolism / Regulatory-Associated Protein of mTOR - antagonists & inhibitors / Regulatory-Associated Protein of mTOR - genetics / Regulatory-Associated Protein of mTOR - metabolism / Ribosomal Protein S6 Kinases, 90-kDa - antagonists & inhibitors / Ribosomal Protein S6 Kinases, 90-kDa - genetics / Ribosomal Protein S6 Kinases, 90-kDa - metabolism / RNA Helicases - metabolism / RNA Interference / RNA Recognition Motif Proteins - metabolism / RNA, Small Interfering - metabolism / Signal transduction / Signal Transduction - drug effects / Stem Cells / TOR protein / TOR Serine-Threonine Kinases - metabolism / Translation / Translation initiation