Molecular control of the amount, subcellular location, and activity state of translation elongation factor 2 in neurons experiencing stress.
Molecular control of the amount, subcellular location, and activity state of translation elongation factor 2 in neurons experiencing stress.
复制标题
在经历压力的神经元中，对量的数量，亚细胞位置和活性状态的分子控制。
DOI：
10.1016/j.freeradbiomed.2013.03.016
复制
发表时间：
2013-08
影响因子：
7.4
通讯作者：
Mattson, Mark P.
中科院分区：
文献类型：
--
作者：
Argueelles, Sandro;Camandola, Simonetta;Hutchison, Emmette R.;Cutler, Roy G.;Ayala, Antonio;Mattson, Mark P.
关键词：
真核细胞延伸因子2（eEF-2）是蛋白质翻译机制的重要调节因子，其中它控制核糖体沿着mRNA的运动。eEF-2的活性受细胞能量状态和营养物质利用率的变化以及翻译后修饰（如磷酸化和单ADP核糖基化）的调节。然而，在神经元细胞应激条件下调节蛋白质翻译的机制尚不清楚。在这里，我们表明，当大鼠海马神经元经历氧化应激（脂质过氧化诱导暴露于氢过氧化枯烯; CH），eEF-2是过度磷酸化和核糖基化导致翻译活性降低。eEF-2的降解需要钙蛋白酶蛋白水解活性，并伴随着eEF-2在核区室中的积累。天然和磷酸化形式的eEF-2的亚细胞定位分别受CRM 1和14.3.3的影响。在海马神经元中，p53与非磷酸化（活性）eEF-2相互作用，但不与其磷酸化形式相互作用。p53 - eEF-2复合物存在于细胞质和细胞核中，当神经元经历氧化应激时，它们的丰度增加。活性eEF-2的核定位取决于其与p53的相互作用，因为缺乏p53的细胞在核区室中含有较少活性的eEF-2。eEF-2在海马神经元中的过度表达导致eEF-2的核水平增加，暴露于CH后细胞死亡减少。我们的研究结果揭示了控制eEF-2的差异亚细胞定位和活性状态的新的分子机制，这可能会影响神经元的生存状态，在氧化应激升高期间。
Eukaryotic elongation factor 2 (eEF-2) is an important regulator of the protein translation machinery wherein it controls the movement of the ribosome along the mRNA. The activity of eEF-2 is regulated by changes in cellular energy status and nutrient availability, and posttranslational modifications such as phosphorylation and mono-ADP-ribosylation. However, the mechanisms regulating protein translation under conditions of cellular stress in neurons are unknown. Here we show that when rat hippocampal neurons experience oxidative stress (lipid peroxidation induced by exposure to cumene hydroperoxide; CH), eEF-2 is hyperphosphorylated and ribosylated resulting in reduced translational activity. The degradation of eEF-2 requires calpain proteolytic activity and is accompanied by accumulation of eEF-2 in the nuclear compartment. The subcellular localization of both native and phosphorylated forms of eEF-2 is influenced by CRM1 and 14.3.3, respectively. In hippocampal neurons p53 interacts with non-phosphorylated (active) eEF-2, but not with its phosphorylated form. The p53 – eEF-2 complexes are present in cytoplasm and nucleus, and their abundance increases when neurons experience oxidative stress. The nuclear localization of active eEF-2 depends upon its interaction with p53, as cells lacking p53 contain less active eEF-2 in the nuclear compartment. Overexpression of eEF-2 in hippocampal neurons results in increased nuclear levels of eEF-2, and decreased cell death following exposure to CH. Our results reveal novel molecular mechanisms controlling the differential subcellular localization and activity state of eEF-2 that may influence the survival status of neurons during periods of elevated oxidative stress.
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DOI：
10.1046/j.1432-1327.1998.2560142.x
发表时间：
1998-08-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bektas, M;Nurten, R;Bermek, E
通讯作者：
Bermek, E
影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
7.4
作者：
Parrado, J;Bougria, M;Machado, A
通讯作者：
Machado, A
影响因子：
10.3
作者：
Argueelles, Sandro;Munoz, Mario F.;Ayala, Antonio
通讯作者：
Ayala, Antonio
影响因子：
3.6
作者：
Bektas, Muhammet;Nurten, Rustem;Bermek, Engin
通讯作者：
Bermek, Engin