Bacterial senescence:: protein oxidation in non-proliferating cells is dictated by the accuracy of the ribosomes
Bacterial senescence:: protein oxidation in non-proliferating cells is dictated by the accuracy of the ribosomes
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DOI：
10.1093/emboj/20.18.5280
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发表时间：
2001-09-17
期刊：
影响因子：
11.4
通讯作者：
Nyström, T
中科院分区：
文献类型：
--
作者：
Ballesteros, M;Fredriksson, Å;Nyström, T
我们研究了细胞增殖过程中与年龄相关的蛋白质氧化背后的原因。蛋白质组学方法表明，在非增殖细胞中，蛋白质氧化主要是在一些异常亚型中产生的蛋白质中观察到的。此外，通过蛋白质组学分析和无义抑制的遗传测量，这些细胞表现出降低的翻译保真度。含有超精确核糖体的突变体在生长停滞期间表现出急剧减弱的蛋白质氧化。相反，在易出错核糖体突变体中，氧化作用增强。氧化作用的增加伴随着翻译速率的降低，这表明异常蛋白和氧化蛋白的产生不是共翻译折叠机制滴定的结果。在高精度rpsL突变体中，与年龄相关的伴侣蛋白DnaK和GroEL的积累急剧减弱，这表明生长受阻细胞中翻译保真度的降低也可能是诱导热休克调控的主要原因。该数据指向了接近真核G(0)细胞中蛋白质氧化的因果因素的另一种方法。
We have investigated the causal factors behind the age-related oxidation of proteins during arrest of cell proliferation. A proteomic approach demonstrated that protein oxidation in non-proliferating cells is observed primarily for proteins being produced in a number of aberrant isoforms. Also, these cells exhibited a reduced translational fidelity as demonstrated by both proteomic analysis and genetic measurements of nonsense suppression. Mutants harboring hyper-accurate ribosomes exhibited a drastically attenuated protein oxidation during growth arrest. In contrast, oxidation was augmented in mutants with error-prone ribosomes. Oxidation increased concomitantly with a reduced rate of translation, indicating that the production of aberrant, and oxidized proteins, is not the result of titration of the co-translational folding machinery. The age-related accumulation of the chaperones, DnaK and GroEL, was drastically attenuated in the hyperaccurate rpsL mutant, demonstrating that the reduced translational fidelity in growth-arrested cells may also be a primary cause for the induction of the heat shock regulon. The data point to an alternative way of approaching the causal factors involved in protein oxidation in eukaryotic G(0) cells.