Functional significance of eIF5A and its hypusine modification in eukaryotes.

Functional significance of eIF5A and its hypusine modification in eukaryotes.
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DOI:
10.1007/s00726-009-0408-7
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发表时间:
2010-02
期刊:
影响因子:
3.5
通讯作者:
Valentini, S. R.
Valentini, S. R.
中科院分区:
生物学3区
文献类型:
--
作者:
Park, M. H.;Nishimura, K.;Zanelli, C. F.;Valentini, S. R.

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不同寻常的碱性氨基酸,苏氨酸[Nε-(4-氨基-2-羟基丁基)-赖氨酸],是一种添加了来自多胺亚精胺的4-氨基丁基的修饰赖氨酸。这种自然产生的氨基酸是一种独特的翻译后修饰的产物,它只出现在一种细胞蛋白中,即真核细胞翻译起始因子5A(eIF5A,eIF-5A)。Hypusine由脱氧亚硫氨酸合成酶(DHS)和脱氧亚硫氨酸羟基酶(DOHH)两步反应合成。脱氧亚精氨酸/亚精氨酸合成途径已在古生物和真核生物中进化,eIF5A、DHS和DOHH高度保守,提示eIF5A具有重要的细胞功能。在酵母和高等真核生物中的基因破坏和突变研究为eIF5A的基本性质以及细胞生长和蛋白质合成中的脱氧亚硫氨酸/亚硫氨酸修饰提供了有价值的信息。鉴于含有亚硫氨酸的eIF5A在哺乳动物细胞增殖中的特殊特异性和功能意义,eIF5A及其生物合成酶是干预异常细胞增殖的新的潜在靶点。
The unusual basic amino acid, hypusine [Nε-(4-amino-2-hydroxybutyl)-lysine], is a modified lysine with the addition of the 4-aminobutyl moiety from the polyamine spermidine. This naturally occurring amino acid is a product of a unique posttranslational modification that occurs in only one cellular protein, eukaryotic translation initiation factor 5A (eIF5A, eIF-5A). Hypusine is synthesized exclusively in this protein by two sequential enzymatic steps involving deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The deoxyhypusine/hypusine synthetic pathway has evolved in archaea and eukaryotes, and eIF5A, DHS and DOHH are highly conserved suggesting a vital cellular function of eIF5A. Gene disruption and mutation studies in yeast and higher eukaryotes have provided valuable information on the essential nature of eIF5A and the deoxyhypusine/hypusine modification in cell growth and in protein synthesis. In view of the extraordinary specificity and functional significance of hypusine-containing eIF5A in mammalian cell proliferation, eIF5A and the hypusine biosynthetic enzymes are novel potential targets for intervention in aberrant cell proliferation.
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