DUG is a novel homologue of translation initiation factor 4G that binds eIF4A

DUG is a novel homologue of translation initiation factor 4G that binds eIF4A
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DOI:
10.1016/s0006-291x(02)02129-0
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发表时间:
2002-09-13
影响因子:
3.1
通讯作者:
Chen, YHH
Chen, YHH
中科院分区:
生物学4区
文献类型:
--
作者:
Göke, A;Göke, R;Chen, YHH

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为了阐明细胞死亡的分子机制,我们从大鼠胰岛素瘤细胞中克隆了一个新的基因,命名为死亡上调基因(DUG)。DUG在正常细胞中以非常低的水平组成表达,但在Fas配体连接血清/葡萄糖饥饿或死亡受体后凋亡细胞中显著上调。DUG mRNA以两种剪接形式存在:长形式编码由469个氨基酸组成的蛋白质,短形式产生由432个氨基酸组成的多肽。预测的DUG蛋白序列包含两个假定的核定位信号,多个蛋白激酶磷酸化位点和两个保守的MA3结构域。重要的是,DUG与真核生物翻译起始因子(eIF) 4G同源,并可能通过MA3结构域与eIF4A结合。转染后,DUG抑制细胞凋亡的内在和外在途径。因此,DUG是eIF4G调控细胞凋亡的新同源物。(C) 2002 Elsevier Science (USA)。版权所有。
To elucidate the molecular mechanisms of cell death, we have cloned a new gene, designated death-upregulated gene (DUG), from rat insulinoma cells. DUG is constitutively expressed at very low levels in normal cells but is dramatically upregulated in apoptotic cells following serum/glucose starvation or death receptor ligation by Fas ligand. The DUG mRNA is present in two splicing forms: a long form that encodes a protein of 469 amino acids and a short form that gives rise to a polypeptide of 432 amino acids. The predicted DUG protein sequence contains two putative nuclear localization signals and multiple phosphorylation sites for protein kinases and two conserved MA3 domains. Importantly, DUG is homologous to eukaryotic translation initiation factor (eIF) 4G and binds to eIF4A presumably through MA3 domains. Upon transfection, DUG inhibits both intrinsic and extrinsic pathways of apoptosis. Thus, DUG is a novel homologue of eIF4G that regulates apoptosis. (C) 2002 Elsevier Science (USA). All rights reserved.