The mTOR-S6 kinase pathway promotes stress granule assembly.
The mTOR-S6 kinase pathway promotes stress granule assembly.
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DOI：
10.1038/s41418-018-0076-9
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发表时间：
2018-11
影响因子：
12.4
通讯作者：
Whitmarsh AJ
中科院分区：
文献类型：
--
作者：
Sfakianos AP;Mellor LE;Pang YF;Kritsiligkou P;Needs H;Abou-Hamdan H;Désaubry L;Poulin GB;Ashe MP;Whitmarsh AJ
应激颗粒是细胞质mRNA-蛋白质复合物，其在抑制翻译起始后形成，并促进细胞响应环境损伤的存活。然而，它们通常与病理学有关，包括神经变性和癌症，并且它们的动态变化与衰老有关。在这里，我们表明mTOR效应激酶S6激酶1（S6 K1）和S6激酶2（S6 K2）定位于人类细胞中的应激颗粒，并且是轻度氧化应激后组装和维持所需的。S6 K1和S6 K2的作用是不同的，其中S6 K1通过调节eIF 2 α磷酸化在应激颗粒的形成中具有更重要的作用，而S6 K2对它们的持久性很重要。In C.在线虫中，S6激酶直向同源物RSKS-1促进应激颗粒的组装，并且其功能的丧失使线虫对应激诱导的死亡敏感。这项研究确定了S6激酶作为应激颗粒动力学的调节剂，并提供了mTOR信号传导，翻译抑制和存活之间的新联系。
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.
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影响因子：
16
作者：
Eisinger-Mathason, T. S. Karin;Andrade, Josefa;Groehler, Angela L.;Clark, David E.;Muratore-Schroeder, Tara L.;Pasic, Lejla;Smith, Jeffrey A.;Shabanowitz, Jeffrey;Hunt, Donald F.;Macara, Ian G.;Lannigan, Deborah A.
通讯作者：
Lannigan, Deborah A.
DOI：
10.1534/g3.115.026815
发表时间：
2016-04-07
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Huelgas-Morales G;Silva-García CG;Salinas LS;Greenstein D;Navarro RE
通讯作者：
Navarro RE
DOI：
10.1073/pnas.0914798107
发表时间：
2010-02-23
影响因子：
11.1
作者：
Li, Shijie;Brown, Michael S.;Goldstein, Joseph L.
通讯作者：
Goldstein, Joseph L.
影响因子：
64.8
作者：
Boussemart, Lise;Malka-Mahieu, Helene;Vagner, Stephan
通讯作者：
Vagner, Stephan
影响因子：
5.3
作者：
Fournier, Marie-Josee;Coudert, Laetitia;Mazroui, Rachid
通讯作者：
Mazroui, Rachid