Morley S J, McKendrick L, Bushell M
Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton, UK.
FEBS Lett. 1998 Oct 30;438(1-2):41-8. doi: 10.1016/s0014-5793(98)01269-1.
Initiation factor (eIF) 4G plays a key role in the regulation of translation, acting as a bridge between eIF4E and eIF3, to allow an mRNA molecule to associate with the 40S ribosomal subunit. In this study, we show that activation of the Fas/CD95 receptor complex in Jurkat cells induces the degradation of eIF4G, the inhibition of total protein synthesis and cell death. These responses were prevented by the caspase inhibitors, zVAD.FMK and zDEVD.FMK. We also show that, in contrast to Saccharomyces cerevisiae, although rapamycin caused a modest inhibition of protein synthesis it did not induce apoptosis or the cleavage of eIF4G. Studies with the specific inhibitor, SB203580, have shown that signalling through the p38 MAP kinase pathway is not required for either the Fas/CD95-induced cleavage of eIF4G or cell death. These data suggest that the cleavage of eIF4G and the inhibition of translation play an integral role in Fas/CD95-induced cell death in Jurkat cells.
起始因子（eIF）4G在翻译调控中起关键作用，它作为eIF4E和eIF3之间的桥梁，使mRNA分子与40S核糖体亚基结合。在本研究中，我们发现Jurkat细胞中Fas/CD95受体复合物的激活会诱导eIF4G降解、抑制总蛋白合成并导致细胞死亡。半胱天冬酶抑制剂zVAD.FMK和zDEVD.FMK可阻止这些反应。我们还发现，与酿酒酵母不同，雷帕霉素虽然对蛋白合成有适度抑制作用，但并未诱导细胞凋亡或eIF4G的裂解。使用特异性抑制剂SB203580的研究表明，Fas/CD95诱导的eIF4G裂解或细胞死亡均不需要通过p38丝裂原活化蛋白激酶途径进行信号传导。这些数据表明，eIF4G的裂解和翻译抑制在Jurkat细胞中Fas/CD95诱导的细胞死亡中起不可或缺的作用。
