The essential vertebrate ABCE1 protein interacts with eukaryotic initiation factors
The essential vertebrate ABCE1 protein interacts with eukaryotic initiation factors
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DOI：
10.1074/jbc.m510603200
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发表时间：
2006-03-17
影响因子：
4.8
通讯作者：
Dean, M
中科院分区：
文献类型：
--
作者：
Chen, ZQ;Dong, JS;Dean, M
ABCE 1基因是ATP结合盒（ABC）多基因家族的成员，由两个核苷酸结合结构域和一个N端Fe-S结合结构域组成。ABCE 1基因编码一种蛋白质，最初被鉴定为抑制核糖核酸酶L，核糖核酸酶L是哺乳动物细胞中由干扰素诱导的核酸酶。该蛋白也是HIV和SIV gag多肽组装所需的。然而，ABCE 1是最高度保守的蛋白质之一，并且在所有表征的真核生物和古细菌中以一个或两个拷贝存在。酵母ABCE 1/RLI 1对细胞分裂至关重要，并在预起始复合物的组装中与翻译起始因子相互作用。我们在这里表明，人ABCE 1蛋白是在体外和体内的mRNA翻译所必需的，它结合eIF 2 α和eIF 5。非洲爪蟾ABCE 1的抑制在原肠胚发育阶段阻止生长，与翻译中的阻断一致。人类ABCE 1基因包含16个内含子，并且其极高程度的氨基酸同一性允许在整个真核生物中检查其内含子的进化。ABCE 1在脊椎动物翻译起始中起作用的证明扩展了这种高度保守蛋白的已知功能。翻译是一个高度调控的过程，对发育和癌症等病理学非常重要，使ABCE 1成为治疗的潜在靶点。进化分析支持一个模型，其中一个祖先的真核生物有大量的内含子和许多这些内含子丢失在非脊椎动物谱系。
The ABCE1 gene is a member of the ATP-binding cassette (ABC) multigene family and is composed of two nucleotide binding domains and an N-terminal Fe-S binding domain. The ABCE1 gene encodes a protein originally identified for its inhibition of ribonuclease L, a nuclease induced by interferon in mammalian cells. The protein is also required for the assembly of the HIV and SIV gag polypeptides. However, ABCE1 is one of the most highly conserved proteins and is found in one or two copies in all characterized eukaryotes and archaea. Yeast ABCE1/RLI1 is essential to cell division and interacts with translation initiation factors in the assembly of the pre-initiation complex. We show here that the human ABCE1 protein is essential for in vitro and in vivo translation of mRNA and that it binds to eIF2 alpha and eIF5. Inhibition of the Xenopus ABCE1 arrests growth at the gastrula stage of development, consistent with a block in translation. The human ABCE1 gene contains 16 introns, and the extremely high degree of amino acid identity allows the evolution of its introns to be examined throughout eukaryotes. The demonstration that ABCE1 plays a role in vertebrate translation initiation extends the known functions of this highly conserved protein. Translation is a highly regulated process important to development and pathologies such as cancer, making ABCE1 a potential target for therapeutics. The evolutionary analysis supports a model in which an ancestral eukaryote had large number of introns and that many of these introns were lost in non-vertebrate lineages.