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DOI | 10.1126/science.abb0993 |
A phosphorylation-regulated eIF3d translation switch mediates cellular adaptation to metabolic stress | |
Adam M. Lamper; Rebecca H. Fleming; Kayla M. Ladd; Amy S. Y. Lee | |
2020-11-13 | |
发表期刊 | Science
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出版年 | 2020 |
英文摘要 | Cells respond to environmental stress by down-regulating general protein synthesis and inducing selective expression of proteins required for survival. However, the mechanisms controlling this selective messenger RNA (mRNA) translation response remain poorly understood. Lamper et al. report that the noncanonical 5′ cap-binding protein subunit eIF3d is activated upon metabolic stress in mammalian cells to reprogram cellular mRNA translation. eIF3d is activated by a switch in phosphorylation status at sites near the cap-binding pocket and enables cells to express the proteins required for the regulation of metabolism and survival during stresses, including glucose starvation. This work reveals how eIF3d-dependent, noncanonical cap-dependent translation controls the cellular adaptation to stress. Science , this issue p. [853][1] Shutoff of global protein synthesis is a conserved response to cellular stresses. This general phenomenon is accompanied by the induction of distinct gene programs tailored to each stress. Although the mechanisms driving repression of general protein synthesis are well characterized, how cells reprogram the translation machinery for selective gene expression remains poorly understood. Here, we found that the noncanonical 5′ cap-binding protein eIF3d was activated in response to metabolic stress in human cells. Activation required reduced CK2-mediated phosphorylation near the eIF3d cap-binding pocket. eIF3d controls a gene program enriched in factors important for glucose homeostasis, including members of the mammalian target of rapamycin (mTOR) pathway. eIF3d-directed translation adaptation was essential for cell survival during chronic glucose deprivation. Thus, this mechanism of translation reprogramming regulates the cellular response to metabolic stress. [1]: /lookup/doi/10.1126/science.abb0993 |
领域 | 气候变化 ; 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/304150 |
专题 | 气候变化 资源环境科学 |
推荐引用方式 GB/T 7714 | Adam M. Lamper,Rebecca H. Fleming,Kayla M. Ladd,et al. A phosphorylation-regulated eIF3d translation switch mediates cellular adaptation to metabolic stress[J]. Science,2020. |
APA | Adam M. Lamper,Rebecca H. Fleming,Kayla M. Ladd,&Amy S. Y. Lee.(2020).A phosphorylation-regulated eIF3d translation switch mediates cellular adaptation to metabolic stress.Science. |
MLA | Adam M. Lamper,et al."A phosphorylation-regulated eIF3d translation switch mediates cellular adaptation to metabolic stress".Science (2020). |
条目包含的文件 | 条目无相关文件。 |
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