Regulation of protein synthesis and the role of eIF3 in cancer
Regulation of protein synthesis and the role of eIF3 in cancer
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DOI：
10.1590/s0100-879x2010001000002
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发表时间：
2010-10-01
影响因子：
2.3
通讯作者：
Hershey, John W.B.
中科院分区：
文献类型：
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作者：
Hershey, John W.B.
维持细胞内稳态和调节细胞增殖的重要依赖于调节蛋白质合成过程。当蛋白质合成失调发生时，许多疾病状态出现。本文综述了翻译调控的机制以及调控异常如何导致细胞恶性肿瘤。大多数翻译控制发生在蛋白质合成的起始阶段，起始因子是通过其磷酸化调节的主要靶点。特别是，通过m（7）G-cap结构募集mRNA和结合起始剂甲硫氨酰-tRNA（i）是常见的靶点。然而，翻译，特别是特定mRNA的翻译，也可以通过螯合到加工体或应激颗粒中、通过反式作用蛋白或通过microRNA来调节。当蛋白质合成过程被过度激活时，弱mRNA的翻译效率相对更高，导致细胞蛋白质的不平衡，从而促进细胞增殖和恶性转化。例如，当帽结合蛋白eIF 4 E过表达时，或当甲硫氨酰-tRNA（i）结合因子eIF 2过于活跃时，就会发生这种情况。此外，增强的eIF 3活性有助于肿瘤发生。翻译起始因子作为蛋白质合成和细胞增殖的重要调节因子，使其成为治疗癌症的潜在靶点。
Maintenance of cell homeostasis and regulation of cell proliferation depend importantly on regulating the process of protein synthesis. Many disease states arise when disregulation of protein synthesis occurs. This review focuses on mechanisms of translational control and how disregulation results in cell malignancy. Most translational controls occur during the initiation phase of protein synthesis, with the initiation factors being the major target of regulation through their phosphorylation. In particular, the recruitment of mRNAs through the m(7)G-cap structure and the binding of the initiator methionyl-tRNA(i) are frequent targets. However, translation, especially of specific mRNAs, may also be regulated by sequestration into processing bodies or stress granules, by trans-acting proteins or by microRNAs. When the process of protein synthesis is hyper-activated, weak mRNAs are translated relatively more efficiently, leading to an imbalance of cellular proteins that promotes cell proliferation and malignant transformation. This occurs, for example, when the cap-binding protein, eIF4E, is overexpressed, or when the methionyl-tRNA(i)-binding factor, eIF2, is too active. In addition, enhanced activity of eIF3 contributes to oncogenesis. The importance of the translation initiation factors as regulators of protein synthesis and cell proliferation makes them potential therapeutic targets for the treatment of cancer.