Caspase-mediated cleavage of eukaryotic translation initiation factor subunit 2alpha.
Caspase-mediated cleavage of eukaryotic translation initiation factor subunit 2alpha.
复制标题
Caspase 介导的真核翻译起始因子亚基 2α 的裂解。
作者：
S. Satoh;M. Hijikata;H. Handa;K. Shimotohno
真核翻译起始因子 2α (eIF-2α) 是干扰素诱导型双链 RNA 依赖性蛋白激酶 (PKR) 的靶分子，在用 Poly(I).poly(C) 或肿瘤坏死因子 α 处理后，在凋亡 Saos-2 细胞中被裂解。这种裂解发生的时间过程与聚（ADP-核糖）聚合酶（一种众所周知的半胱天冬酶底物）的时间过程相似。此外，eIF-2alpha 在体外被重组活性 caspase-3 裂解。通过定点诱变，切割位点被定位到位于 eIF-2α C 末端部分的 Ala-Glu-Val-Asp(300) 向下箭头 Gly(301) 序列。 PKR 磷酸化 Ser(51) 上的 eIF-2alpha，从而抑制蛋白质合成。当 eIF-2α C 末端裂解产物在 Saos-2 细胞中过表达时，PKR 介导的翻译抑制受到抑制，尽管 PKR 可以磷酸化该裂解产物。这些结果表明 caspase-3 或相关蛋白酶可以通过切割 eIF-2 的 α 亚基（翻译起始中的关键成分）来调节蛋白质合成的效率。
Eukaryotic translation initiation factor 2alpha (eIF-2alpha), a target molecule of the interferon-inducible double-stranded-RNA-dependent protein kinase (PKR), was cleaved in apoptotic Saos-2 cells on treatment with poly(I).poly(C) or tumour necrosis factor alpha. This cleavage occurred with a time course similar to that of poly(ADP-ribose) polymerase, a well-known caspase substrate. In addition, eIF-2alpha was cleaved by recombinant active caspase-3 in vitro. By site-directed mutagenesis, the cleavage site was mapped to an Ala-Glu-Val-Asp(300) downward arrowGly(301) sequence located in the C-terminal portion of eIF-2alpha. PKR phosphorylates eIF-2alpha on Ser(51), resulting in the suppression of protein synthesis. PKR-mediated translational suppression was repressed when the C-terminally cleaved product of eIF-2alpha was overexpressed in Saos-2 cells, even though PKR can phosphorylate this cleaved product. These results suggest that caspase-3 or related protease(s) can modulate the efficiency of protein synthesis by cleaving the alpha subunit of eIF-2, a key component in the initiation of translation.