真核延伸因子 2 激酶通过阻断翻译延伸赋予细胞抵抗营养缺乏的能力。
The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation.
机构信息
Department of Molecular Oncology, British Columbia Cancer Research Centre, University of British Columbia (UBC), Vancouver, BC V5Z1L4, Canada.
出版信息
Cell. 2013 May 23;153(5):1064-79. doi: 10.1016/j.cell.2013.04.055.
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. PAPERCLIP:
代谢适应对于营养剥夺期间细胞的存活至关重要。我们报告称，真核延伸因子 2 激酶（eEF2K）可被 AMP 激酶（AMPK）激活，通过阻断翻译延伸赋予细胞在急性营养缺乏下的存活能力。肿瘤细胞通过重新激活 AMPK-eEF2K 轴来适应营养剥夺。缺乏 eEF2K 的细胞中，转化细胞对营养剥夺的适应能力严重受损。此外，eEF2K 的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，eEF2K 的过表达使小鼠肿瘤对热量限制具有显著的抗性。eEF2K 的表达与人成神经管细胞瘤和多形性胶质母细胞瘤的总生存期强烈相关。最后，缺乏 eEF2K 直系同源物 efk-1 的 C. elegans 品系在对营养缺乏的反应中严重受损。我们的数据强调了 eEF2K 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。
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