Perk is essential for translational regulation and cell survival during the unfolded protein response
Perk is essential for translational regulation and cell survival during the unfolded protein response
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DOI：
10.1016/s1097-2765(00)80330-5
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发表时间：
2000-05-01
期刊：
影响因子：
16
通讯作者：
Ron, D
中科院分区：
文献类型：
--
作者：
Harding, HP;Zhang, YH;Ron, D
内质网（ER）中的错误折叠蛋白抑制翻译起始。这种反应被认为是由真核起始因子2 α（eIF2 α）的磷酸化增加介导的，并被假设为减少应激期间施加在折叠机器上的工作负荷。在这里，我们报告，突变的基因编码的ER应激激活eIF2 α激酶PERK废除eIF2 α的磷酸化响应错误折叠的蛋白质在ER中的积累，导致异常升高的蛋白质合成和更高水平的ER应激。突变体细胞在ER应激中存活的能力明显受损，在ER应激期间通过放线菌酮处理抑制蛋白质合成改善了这种损害。因此，PERK在细胞适应ER应激的能力中起着重要作用。
Malfolded proteins in the endoplasmic reticulum (ER) inhibit translation initiation. This response is believed to be mediated by increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2 alpha) and is hypothesized to reduce the work load imposed on the folding machinery during stress. Here we report that mutating the gene encoding the ER stress-activated eIF2 alpha kinase PERK abolishes the phosphorylation of eIF2 alpha in response to accumulation of malfolded proteins in the ER resulting in abnormally elevated protein synthesis and higher levels of ER stress. Mutant cells are markedly impaired in their ability to survive ER stress and inhibition of protein synthesis by cycloheximide treatment during ER stress ameliorates this impairment. PERK thus plays a major role in the ability of cells to adapt to ER stress.