Controlling gene expression through RNA regulons - The role of the eukaryotic translation initiation factor eIF4E
Controlling gene expression through RNA regulons - The role of the eukaryotic translation initiation factor eIF4E
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DOI：
10.4161/cc.6.1.3688
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发表时间：
2007-01-01
期刊：
影响因子：
4.3
通讯作者：
Borden, Katherine L. B.
中科院分区：
文献类型：
--
作者：
Culjkovic, Biljana;Topisirovic, Ivan;Borden, Katherine L. B.
真核翻译起始因子 eIF4E 是一种强癌基因。 1 事实上，它在人类癌症中的过度表达通常与不良预后相关。 1,2 传统上，eIF4E 在翻译起始中发挥作用，它与 mRNA 上的 5' m(7)G 帽结合。(3) 最近的研究表明，很大一部分 eIF4E（高达 68%）驻留在细胞核中，在细胞核中调节特定 mRNA 的核输出。此外，eIF4E 可能在细胞质加工体（P 体）中的 mRNA 隔离和稳定性中发挥作用。 4,5 我们最近的研究表明，eIF4E 通过在转录后水平协调多个基因的表达来控制细胞周期进程和细胞增殖。因此，eIF4E 作为 RNA 调节子（如下所述）的中心节点发挥作用，该调节子在正常分化和发育中发挥重要作用，并且在癌症中经常失调。一些细胞因子，例如早幼粒细胞白血病蛋白 PML，通过改变 eIF4E 的活性来调节该调节子的功能。在此，描述了这些观察结果的生理学意义，并讨论了直接靶向 eIF4E 和相关调节子的临床意义。
The eukaryotic translation initiation factor eIF4E is a potent oncogene. 1 In fact, its overexpression in human cancer often correlates with poor prognosis. 1,2 Traditionally, eIF4E plays a role in translation initiation where it binds the 5' m(7)G cap found on mRNAs.(3) More recent studies indicate that a significant fraction of eIF4E (up to 68%) resides in the nucleus where it regulates the nuclear export of specific mRNAs. Additionally, eIF4E may play a role in mRNA sequestration and stability in cytoplasmic processing bodies (P-bodies). 4,5 Our recent studies suggest that eIF4E governs cell cycle progression and cellular proliferation by coordinately orchestrating the expression of several genes at the post-transcriptional level. Hence, eIF4E functions as a central node of an RNA regulon (described below), which plays an essential role in normal differentiation and development and is frequently dysregulated in cancer. Several cellular factors, such as the promyelocytic leukemia protein PML, modulate the function of this regulon by altering the activity of eIF4E. Here, the physiological implications of these observations are described and the clinical implications of directly targeting eIF4E, and the related regulon, are discussed.