Inactivation of eIF2B and phosphorylation of PHAS-I in heat-shocked rat hepatoma cells
Inactivation of eIF2B and phosphorylation of PHAS-I in heat-shocked rat hepatoma cells
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DOI：
10.1074/jbc.272.43.26850
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发表时间：
1997-10-24
影响因子：
4.8
通讯作者：
vanWijk, R
中科院分区：
文献类型：
--
作者：
Scheper, GC;Mulder, J;vanWijk, R
热休克诱导的蛋白质合成抑制中涉及多种因素，已经显示了几种细胞类型在热休克时磷酸化的变化，导致真核起始因子（eIF）eIF 2和eIF 4 E的失活，然而，在哺乳动物细胞中，这些变化发生在43 ℃或更高的温度下，而蛋白质合成在较温和的热休克温度下已经受到影响，在寻找鹤的蛋白质合成的抑制，eIF 2和eIF 4 E的调节通过额外的因素进行了分析。在这方面，在热震荡期间和之后测量eIF 2B的活性。一个非常明确的相关性，发现这种鸟嘌呤交换因子的活性和蛋白质合成的水平之间，也在温和的热休克条件。还分析了eIF 4 E和eIF 4 E结合蛋白PHAS-I磷酸化的变化。令人惊讶的是，在H35细胞以及一些其他细胞系中，热休克增加了PHAS-I磷酸化，而在其他细胞系中则减少了PHAS-I磷酸化。因此，在应激条件下减少eIF 4 E的可用性似乎并不是抑制蛋白质合成的一般机制热休克，调节eIF 2B活性似乎是在温和温度下热休克后控制翻译起始的主要机制。
Various factors are involved in the heat shock-induced inhibition of protein synthesis, Changes upon heat shock in phosphorylation, leading to inactivation, of eukaryotic initiation factors (eIFs) eIF2 and eIF4E have been shown for several cell types, However, in mammalian cells these changes occur at temperatures of 43 degrees C or higher while protein synthesis is already affected at milder heat shock temperatures, In searching far the cranes for the inhibition of protein synthesis, the regulation of eIF2 and eIF4E by additional factors was analyzed. In this respect, the activity of eIF2B was measured during and after heat shook. A very clear correlation was found between the activity of this guanine exchange factor and the levels of protein synthesis, also at mild heat shock conditions. Changes in the phosphorylation of eIF4E and of the eIF4E-binding protein PHAS-I were also analyzed. Surprisingly, in H35 cells as well as in some other cell lines, PHAS-I phosphorylation was increased by heat shock, whereas in others it was decreased, Therefore, decreasing the eIF4E availability under stressful conditions does not seem to be a general mechanism to inhibit protein synthesis by heat shack, Regulation of eIF2B activity appears to be the main mechanism to control translation initiation after heat shock at mild temperatures.