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首页> 外文期刊>Molecular cell >Translational control is required for the unfolded protein response and in vivo glucose homeostasis.
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Translational control is required for the unfolded protein response and in vivo glucose homeostasis.

机译:对于未折叠的蛋白质反应和体内葡萄糖稳态,需要翻译控制。

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摘要

The accumulation of unfolded protein in the endoplasmic reticulum (ER) attenuates protein synthesis initiation through phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) at Ser51. Subsequently, transcription of genes encoding adaptive functions including the glucose-regulated proteins is induced. We show that eIF2alpha phosphorylation is required for translation attenuation, transcriptional induction, and survival in response to ER stress. Mice with a homozygous mutation at the eIF2alpha phosphorylation site (Ser51Ala) died within 18 hr after birth due to hypoglycemia associated with defective gluconeogenesis. In addition, homozygous mutant embryos and neonates displayed a deficiency in pancreatic beta cells. The results demonstrate that regulation of translation through eIF2alpha phosphorylation is essential for the ER stress response and in vivo glucose homeostasis.
机译:内质网(ER)中未折叠蛋白的积累通过在Ser51处真核翻译起始因子2(eIF2alpha)的α亚基的磷酸化来减弱蛋白质合成的起始。随后,诱导编码包括葡萄糖调节蛋白的适应性功能的基因的转录。我们表明,eIF2alpha磷酸化是翻译衰减,转录诱导和对内质网应激反应的存活所必需的。在eIF2alpha磷酸化位点(Ser51Ala)具有纯合突变的小鼠在出生后18小时内因与糖异生不良相关的低血糖而死亡。此外,纯合突变的胚胎和新生儿显示出胰腺β细胞的缺乏。结果表明,通过eIF2alpha磷酸化调节翻译对于内质网应激反应和体内葡萄糖稳态是必不可少的。

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