A phosphorylation-regulated eIF3d translation switch mediates cellular adaptation to metabolic stress

doi:10.1126/science.abb0993

GSTDTAP > 气候变化

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
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	被引频次：51[WOS] [WOS记录] [WOS相关记录]
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).