Cap-independent regulation of gene expression in apoptosis
Cap-independent regulation of gene expression in apoptosis
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DOI：
10.1039/b708867a
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发表时间：
2007-01-01
影响因子：
--
通讯作者：
Holcik, Martin
中科院分区：
文献类型：
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作者：
Graber, Tyson E.;Holcik, Martin
蛋白质组的表达在蛋白质合成水平上受到严格调控。翻译控制是一种关键的稳态机制，允许细胞在面对不断变化的细胞内和细胞外环境时快速改变其表型。越来越清楚的是，当涉及到细胞应激期间的蛋白质翻译时，并非所有mrna都被平等对待。大多数mrna的翻译在诱导程序性细胞死亡（如缺氧或DNA损伤）的细胞应激过程中受到损害。然而，细胞信息在其59个未翻译区域内含有内部核糖体进入位点元件（IRES），对应激诱导的全局翻译抑制不敏感。相反，这些含有ires的mrna使用一种鲜为人知的替代翻译机制，允许细胞从短暂应激中恢复或沿着凋亡死亡的路径继续表达所需的蛋白质。这篇综述将重点介绍最近的文献，这些文献表明为什么在应激和细胞凋亡期间，全局翻译率会受到损害，以及这些条件如何介导相关蛋白质合成机制的开关。此外，我们将对ires介导的翻译在细胞应激诱导的细胞凋亡和人类疾病中的生理作用和机制的最新进展进行研究。
Expression of the proteome is tightly regulated at the level of protein synthesis. Translational control is a critical homeostatic mechanism that allows the cell to rapidly change its phenotype in the face of an intra- and extra-cellular environment in constant flux. It is becoming increasingly clear that when it comes to protein translation during cell stress, all mRNAs are not treated equally. The translation of the majority of mRNAs is compromised during cell stresses that induce programmed cell death such as hypoxia, or DNA damage. However, cellular messages harbouring Internal Ribosome Entry Site elements (IRES) within their 59 untranslated regions are insensitive to stress-induced repression of global translation. Instead, these IRES-containing mRNAs use a poorly understood alternative mechanism of translation that allows continued expression of proteins that are required for the cell to recover from a transient stress or to proceed down the path toward apoptotic death. This review will highlight recent literature that suggests why global translation rates are impaired during stress and apoptosis and how these conditions mediate a switch in the mechanism by which pertinent proteins are synthesized. In addition, recent advances towards our understanding of the physiological role and mechanism of IRES-mediated translation in the context of cell stress-induced apoptosis and human disease will be examined.