The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation.
The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation.
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EEF2激酶通过阻止翻译伸长来赋予对营养剥夺的耐药性。
DOI：
10.1016/j.cell.2013.04.055
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发表时间：
2013-05-23
期刊：
影响因子：
64.5
通讯作者：
Sorensen PH
中科院分区：
文献类型：
--
作者：
Leprivier G;Remke M;Rotblat B;Dubuc A;Mateo AR;Kool M;Agnihotri S;El-Naggar A;Yu B;Somasekharan SP;Faubert B;Bridon G;Tognon CE;Mathers J;Thomas R;Li A;Barokas A;Kwok B;Bowden M;Smith S;Wu X;Korshunov A;Hielscher T;Northcott PA;Galpin JD;Ahern CA;Wang Y;McCabe MG;Collins VP;Jones RG;Pollak M;Delattre O;Gleave ME;Jan E;Pfister SM;Proud CG;Derry WB;Taylor MD;Sorensen PH
代谢适应是细胞在营养缺乏时生存所必需的。我们报告，真核细胞延伸因子2激酶（eEF 2K），这是激活的AMP激酶（AMPK），赋予细胞生存急性营养耗竭通过阻断翻译延伸。肿瘤细胞利用该途径通过重新激活AMPK-eEF 2K轴来适应营养剥夺。在缺乏eEF 2K的细胞中，转化细胞对营养素去除的适应性严重受损。此外，eEF 2K敲低恢复了高度耐药的人类肿瘤细胞系对急性营养剥夺的敏感性。在体内，eEF 2K的过度表达使小鼠肿瘤对热量限制具有显著抗性。eEF 2K的表达与人髓母细胞瘤和多形性胶质母细胞瘤的总生存率密切相关。最后，C.缺乏efk-1（eEF 2K直系同源物）的线虫菌株在它们对营养物消耗的反应中严重受损。我们的数据强调了eEF 2K在保护细胞免受营养剥夺和赋予肿瘤细胞适应代谢应激方面的保守作用。
Metabolic adaptation is essential for cell survival during nutrient deprivation. We report that eukaryotic elongation factor 2 kinase (eEF2K), which is activated by AMP-kinase (AMPK), confers cell survival under acute nutrient depletion by blocking translation elongation. Tumor cells exploit this pathway to adapt to nutrient deprivation by reactivating the AMPK-eEF2K axis. Adaptation of transformed cells to nutrient withdrawal is severely compromised in cells lacking eEF2K. Moreover, eEF2K knockdown restored sensitivity to acute nutrient deprivation in highly resistant human tumor cell lines. In vivo, overexpression of eEF2K rendered murine tumors remarkably resistant to caloric restriction. Expression of eEF2K strongly correlated with overall survival in human medulloblastoma and glioblastoma multiforme. Finally, C. elegans strains deficient in efk-1, the eEF2K ortholog, were severely compromised in their response to nutrient depletion. Our data highlight a conserved role for eEF2K in protecting cells from nutrient deprivation and in conferring tumor cell adaptation to metabolic stress.
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