Essential role of eIF5A-1 and deoxyhypusine synthase in mouse embryonic development.
Essential role of eIF5A-1 and deoxyhypusine synthase in mouse embryonic development.
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DOI：
10.1007/s00726-011-0986-z
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发表时间：
2012-02
期刊：
影响因子：
3.5
通讯作者：
Park, Myung Hee
中科院分区：
文献类型：
--
作者：
Nishimura, Kazuhiro;Lee, Seung Bum;Park, Jong Hwan;Park, Myung Hee
真核起始因子5A （eIF5A）含有一种多胺衍生的氨基酸，hypusine [Nε-（4-氨基-2-羟基丁基）赖氨酸]。Hypusine是翻译后由多胺亚精胺中的4-氨基丁基部分加入到特定赖氨酸残基上，由脱氧Hypusine合酶（DHPS）催化，随后由脱氧Hypusine羟化酶（DOHH）羟基化而形成的。eIF5A前体蛋白及其两种修饰酶高度保守，表明eIF5A及其hypusine修饰具有重要的细胞功能。为了研究eIF5A和第一种修饰酶DHPS在哺乳动物发育中的功能，我们在小鼠中敲除了eIF5A或DHPS基因。Eif5a型杂合敲除小鼠和Dhps型杂合敲除小鼠均可存活和生育。而纯合子Eif5a1 gt/gt胚胎和Dhps gt/gt胚胎在E3.5 ~ E7.5之间早期死亡。转移到离体培养后，E3.5的纯合子Eif5a gt/gt或Dhps gt/gt囊胚与杂合子或野生型囊胚相比，出现生长缺陷。因此，敲除Eif5a -1基因（Eif5a）或脱氧hypusine合酶基因（Dhps）都会导致小鼠早期胚胎死亡，这表明Eif5a -1和脱氧hypusine合酶在哺乳动物发育中的重要作用。
The eukaryotic initiation factor 5A (eIF5A) contains a polyamine-derived amino acid, hypusine [Nε-(4-amino-2-hydroxybutyl)lysine]. Hypusine is formed post-translationally by the addition of the 4-aminobutyl moiety from the polyamine spermidine to a specific lysine residue, catalyzed by deoxyhypusine synthase (DHPS), and by subsequent hydroxylation by deoxyhypusine hydroxylase (DOHH). The eIF5A precursor protein and both of its modifying enzymes are highly conserved, suggesting a vital cellular function for eIF5A and its hypusine modification. To address the functions of eIF5A and the first modification enzyme, DHPS, in mammalian development, we knocked out the Eif5a or the Dhps gene in mice. Eif5a heterozygous knockout mice and Dhps heterozygous knockout mice were viable and fertile. However, homozygous Eif5a1 gt/gt embryos and Dhps gt/gt embryos died early in embryonic development, between E3.5 and E7.5. Upon transfer to in vitro culture, homozygous Eif5a gt/gt or Dhps gt/gt blastocysts at E3.5 showed growth defects when compared to heterozygous or wild type blastocysts. Thus, the knockout of either the eIF5A-1 gene (Eif5a) or of the deoxyhypusine synthase gene (Dhps) caused early embryonic lethality in mice, indicating the essential nature of both eIF5A-1 and deoxyhypusine synthase in mammalian development.
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影响因子：
4.1
作者：
Nishimura, K;Murozumi, K;Igarashi, K
通讯作者：
Igarashi, K
DOI：
10.1016/j.bbrc.2009.01.148
发表时间：
2009-03-20
影响因子：
3.1
作者：
Gregio, Ana P. B.;Cano, Veridiana P. S.;Zanelli, Cleslei F.
通讯作者：
Zanelli, Cleslei F.
环吡酮和去铁酮抑制 HIV-1 基因表达，这两种药物可防止真核起始因子 5A 的兴奋作用。
影响因子：
3.3
作者：
Hoque, Mainul;Hanauske-Abel, Hartmut M.;Palumbo, Paul;Saxena, Deepti;Gandolfi, Darlene D'Alliessi;Park, Myung Hee;Pe'ery, Tsafi;Mathews, Michael B.
通讯作者：
Mathews, Michael B.
影响因子：
3.5
作者：
Park, M. H.;Nishimura, K.;Zanelli, C. F.;Valentini, S. R.
通讯作者：
Valentini, S. R.
影响因子：
4
作者：
Jao, DLE;Chen, KY
通讯作者：
Chen, KY