Cleavage of translation initiation factor 4G (eIF4G) during anti-Fas IgM-induced apoptosis does not require signalling through the p38 mitogen-activated protein (MAP) kinase
Cleavage of translation initiation factor 4G (eIF4G) during anti-Fas IgM-induced apoptosis does not require signalling through the p38 mitogen-activated protein (MAP) kinase
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DOI：
10.1016/s0014-5793(98)01269-1
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发表时间：
1998-10-30
期刊：
影响因子：
3.5
通讯作者：
Bushell, M
中科院分区：
文献类型：
--
作者：
Morley, SJ;McKendrick, L;Bushell, M
起始因子(EIF)4G在翻译调控中起着关键作用，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受体复合体的激活导致eIF4G的降解，总蛋白合成的抑制和细胞的死亡。这些反应被caspase抑制剂zVAD.FMK和zDEVD.FMK阻止。我们还表明，与酿酒酵母不同的是，尽管雷帕霉素引起蛋白质合成的适度抑制，但它不诱导细胞凋亡或eIF4G的裂解，使用特异性抑制剂SB203580的研究表明，无论是Fas/CD95诱导的eIF4G的裂解或细胞死亡，都不需要通过p38 MAPK途径的信号，这些数据表明eIF4G的裂解和翻译的抑制在Fas/CD95诱导的Jurkat细胞死亡中起着不可或缺的作用。(C)1998年欧洲生化学会联合会。
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. (C) 1998 Federation of European Biochemical Societies.