The translation factor eIF5A and human cancer.
The translation factor eIF5A and human cancer.
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DOI：
10.1016/j.bbagrm.2015.05.002
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Hershey JW
中科院分区：
文献类型：
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作者：
Mathews MB;Hershey JW
真核生物起始因子eIF5A是一种翻译因子，其在起始和延伸中均被赋予功能。此外，它还参与转录、mRNA周转和核质转运。两种eIF5A亚型由不同但相关的基因产生。主要同种型eIF5A1被认为是组成型的，在大多数细胞中大量表达，并且对于细胞增殖是必需的。第二种亚型eIF5A2在少数正常组织中表达，但在许多癌症中高度表达，并已被指定为候选癌基因。任何一种亚型的表达升高都会对几种癌症产生不利的预后影响，两者都已作为癌症生物标志物得到发展。氨基酸羟腐胺赖氨酸是一种推定独特的eIF 5A翻译后修饰，是大多数已知的eIF 5A功能所需的，并且它使eIF 5A容易受到作为治疗靶点的修饰途径抑制剂的影响。eIF5A已被证明可以特异性地调节许多基因产物，称为eIF5A调节子，并且其在翻译富含脯氨酸的序列中的作用最近已被鉴定。先进的模型，可容纳eIF5A在启动和延长阶段的翻译。本文综述了eIF5A的生物化学功能、其亚型与人类癌症的关系以及临床应用的进展。
The eukaryotic initiation factor eIF5A is a translation factor that, unusually, has been assigned functions in both initiation and elongation. Additionally, it is implicated in transcription, mRNA turnover and nucleocytoplasmic transport. Two eIF5A isoforms are generated from distinct but related genes. The major isoform, eIF5A1, is considered constitutive, is abundantly expressed in most cells, and is essential for cell proliferation. The second isoform, eIF5A2, is expressed in few normal tissues but is highly expressed in many cancers and has been designated a candidate oncogene. Elevated expression of either isoform carries unfavorable prognostic implications for several cancers, and both have been advanced as cancer biomarkers. The amino acid hypusine, a presumptively unique eIF5A post-translational modification, is required for most known eIF5A functions and it renders eIF5A susceptible to inhibitors of the modification pathway as therapeutic targets. eIF5A has been shown to regulate a number of gene products specifically, termed the eIF5A regulon, and its role in translating proline-rich sequences has recently been identified. A model is advanced that accommodates eIF5A in both the initiation and elongation phases of translation. We review here the biochemical functions of eIF5A, the relationship of its isoforms with human cancer, and evolving clinical applications.