Nutrient Deprivation Elicits a Transcriptional and Translational Inflammatory Response Coupled to Decreased Protein Synthesis.
Nutrient Deprivation Elicits a Transcriptional and Translational Inflammatory Response Coupled to Decreased Protein Synthesis.
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DOI：
10.1016/j.celrep.2018.07.021
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发表时间：
2018-08-07
期刊：
影响因子：
8.8
通讯作者：
Struhl K
中科院分区：
文献类型：
--
作者：
Gameiro PA;Struhl K
营养剥夺通过mTOR和eIF2α信号抑制mRNA翻译，但目前尚不清楚如何控制翻译程序以反映代谢应激的程度。在乳腺细胞转化模型中，各种形式的营养剥夺对蛋白质合成及其恢复的影响不同。谷氨酰胺缺失细胞的全基因组翻译分析揭示了含有uORFs的mrna的快速上调和核糖体蛋白mrna的下调，随后是细胞因子和炎症mrna的选择性翻译。炎症和细胞因子基因的转录和翻译在不同的代谢应激下受到刺激，并依赖于eIF2α磷酸化，刺激程度与整体蛋白质合成的减少有关。与炎症刺激一致，谷氨酰胺剥夺刺激转化细胞的迁移。因此，促炎基因表达与代谢应激相耦合，这可以在营养限制下影响癌细胞的行为。某些营养物质的剥夺可能比其他营养物质对mRNA翻译施加更多的限制。Gameiro和Struhl描述了在各种代谢应激反应中翻译抑制和促炎基因表达之间的关系。促炎转录和翻译反应本身不是由mTOR抑制触发的，而是需要eIF2α磷酸化。
Nutrient deprivation inhibits mRNA translation through mTOR and eIF2α signaling, but it is unclear how the translational program is controlled to reflect the degree of a metabolic stress. In a model of breast cellular transformation, various forms of nutrient deprivation differentially affect the rate of protein synthesis and its recovery over time. Genome-wide translational profiling of glutamine-deprived cells reveals a rapid upregulation of mRNAs containing uORFs and downregulation of ribosomal protein mRNAs, which are followed by selective translation of cytokine and inflammatory mRNAs. Transcription and translation of inflammatory and cytokine genes are stimulated in response to diverse metabolic stresses and depend on eIF2α phosphorylation, with the extent of stimulation correlating with the decrease in global protein synthesis. In accord with the inflammatory stimulus, glutamine deprivation stimulates the migration of transformed cells. Thus, pro-inflammatory gene expression is coupled to metabolic stress, and this can affect cancer cell behavior upon nutrient limitation. Deprivation of some nutrients may impose more constraints on mRNA translation than others. Gameiro and Struhl describe a relationship between translational repression and pro-inflammatory gene expression in response to various metabolic stresses. The pro-inflammatory transcriptional and translational response is not triggered by mTOR inhibition, per se, and requires eIF2α phosphorylation.
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影响因子：
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作者：
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发表时间：
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