Clemens M J, Bushell M, Jeffrey I W, Pain V M, Morley S J
Department of Biochemistry and Immunology, Cellular and Molecular Sciences Group, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK.
Cell Death Differ. 2000 Jul;7(7):603-15. doi: 10.1038/sj.cdd.4400695.
The rate of protein synthesis is rapidly down-regulated in mammalian cells following the induction of apoptosis. Inhibition occurs at the level of polypeptide chain initiation and is accompanied by the phosphorylation of the alpha subunit of initiation factor eIF2 and the caspase-dependent cleavage of initiation factors eIF4G, eIF4B, eIF2alpha and the p35 subunit of eIF3. Proteolytic cleavage of these proteins yields characteristic products which may exert regulatory effects on the translational machinery. Inhibition of caspase activity protects protein synthesis from long-term inhibition in cells treated with some, but not all, inducers of apoptosis. This review describes the initiation factor modifications and the possible signalling pathways by which translation may be regulated during apoptosis. We discuss the significance of the initiation factor cleavages and other changes for protein synthesis, and the implications of these events for our understanding of the cellular changes associated with apoptosis.
在哺乳动物细胞中，凋亡诱导后蛋白质合成速率迅速下调。抑制作用发生在多肽链起始水平，并伴随着起始因子eIF2的α亚基磷酸化以及起始因子eIF4G、eIF4B、eIF2α和eIF3的p35亚基的半胱天冬酶依赖性切割。这些蛋白质的蛋白水解切割产生特征性产物，可能对翻译机制发挥调节作用。半胱天冬酶活性的抑制可保护蛋白质合成免受某些（但不是所有）凋亡诱导剂处理的细胞中的长期抑制。本综述描述了起始因子修饰以及在凋亡过程中翻译可能受到调控的潜在信号通路。我们讨论了起始因子切割和其他变化对蛋白质合成的意义，以及这些事件对我们理解与凋亡相关的细胞变化的影响。
