Transcriptional regulation of gene expression during osmotic stress responses by the mammalian target of rapamycin.
Transcriptional regulation of gene expression during osmotic stress responses by the mammalian target of rapamycin.
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DOI：
10.1093/nar/gks038
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发表时间：
2012-05
影响因子：
14.9
通讯作者：
Aramburu J
中科院分区：
文献类型：
--
作者：
Ortells MC;Morancho B;Drews-Elger K;Viollet B;Laderoute KR;López-Rodríguez C;Aramburu J
虽然压力可以抑制生长和增殖，但细胞可以诱导适应性反应，使它们在压力下维持这些功能。虽然许多研究都集中在应激对细胞生长的抑制作用上，但对于促进生长的途径如何影响应激反应却知之甚少。我们通过分析中枢生长控制因子雷帕霉素靶标(MTOR)对渗透胁迫反应的影响来探讨这个问题。我们的结果表明，暴露在中等高张状态下的哺乳动物细胞保持活跃的mTOR，这是维持其细胞大小和增殖能力所必需的。此外，mTOR调控不同渗透压反应基因的诱导，包括张力反应转录因子NFAT5的靶标以及NFAT5不依赖的基因。对mTOR敏感的基因包括应激反应、生长和增殖的调节因子。其中，我们鉴定了Redd1和REDD2，它们以前被认为是在其他应激环境中的mTOR抑制物。我们观察到，mTOR通过促进组蛋白H4乙酰化和RNA聚合酶II的募集，促进了几个渗透压反应基因的转录允许条件。总之，这些结果揭示了mTOR在调节转录机制中的作用，这些转录机制在细胞应激反应中控制基因的表达。
Although stress can suppress growth and proliferation, cells can induce adaptive responses that allow them to maintain these functions under stress. While numerous studies have focused on the inhibitory effects of stress on cell growth, less is known on how growth-promoting pathways influence stress responses. We have approached this question by analyzing the effect of mammalian target of rapamycin (mTOR), a central growth controller, on the osmotic stress response. Our results showed that mammalian cells exposed to moderate hypertonicity maintained active mTOR, which was required to sustain their cell size and proliferative capacity. Moreover, mTOR regulated the induction of diverse osmostress response genes, including targets of the tonicity-responsive transcription factor NFAT5 as well as NFAT5-independent genes. Genes sensitive to mTOR-included regulators of stress responses, growth and proliferation. Among them, we identified REDD1 and REDD2, which had been previously characterized as mTOR inhibitors in other stress contexts. We observed that mTOR facilitated transcription-permissive conditions for several osmoresponsive genes by enhancing histone H4 acetylation and the recruitment of RNA polymerase II. Altogether, these results reveal a previously unappreciated role of mTOR in regulating transcriptional mechanisms that control gene expression during cellular stress responses.
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影响因子：
3.7
作者：
Drews-Elger K;Ortells MC;Rao A;López-Rodriguez C;Aramburu J
通讯作者：
Aramburu J
影响因子：
4.8
作者：
Dmitrieva, N;K端ltz, D;Burg, M
通讯作者：
Burg, M
影响因子：
3.3
作者：
BOUCHER, RC;STUTTS, MJ;GATZY, JT
通讯作者：
GATZY, JT
影响因子：
16
作者：
Düvel K;Yecies JL;Menon S;Raman P;Lipovsky AI;Souza AL;Triantafellow E;Ma Q;Gorski R;Cleaver S;Vander Heiden MG;MacKeigan JP;Finan PM;Clish CB;Murphy LO;Manning BD
通讯作者：
Manning BD
DOI：
10.1016/s1095-6433(01)00439-1
发表时间：
2001-10-01
影响因子：
2.3
作者：
Dmitrieva, NI;Michea, LF;Burg, MB
通讯作者：
Burg, MB