Drosophila Cup is an eIF4E-binding protein that functions in Smaug-mediated translational repression

Drosophila Cup is an eIF4E-binding protein that functions in Smaug-mediated translational repression
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DOI:
10.1038/sj.emboj.7600026
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发表时间:
2004-01-14
期刊:
影响因子:
11.4
通讯作者:
Smibert, CA
Smibert, CA
中科院分区:
生物学1区
文献类型:
--
作者:
Nelson, MR;Leidal, AM;Smibert, CA

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翻译调控在发育过程中起着至关重要的作用,通常涉及与特定mrna的30个非翻译区(UTR)序列相互作用的因子。例如,果蝇胚胎后部的Nanos蛋白指导后向发育,而这种定位需要对后定位的Nanos mRNA进行选择性翻译。纳米翻译的空间调控需要Smaug蛋白与纳米30 UTR结合,抑制非定位纳米转录物的翻译。虽然30种utr结合的翻译调节因子的功能通常知之甚少,但它们可能与基本的翻译机制相互作用。在这里,我们证明Smaug与Cup蛋白相互作用,Cup是一种eIF4E结合蛋白,阻断eIF4G与eIF4E的结合。Cup介导Smaug和eIF4E之间的间接相互作用,Smaug在体内的功能需要Cup。因此,Smaug在eIF4G的募集中通过cup依赖的阻滞抑制翻译。
Translational regulation plays an essential role in development and often involves factors that interact with sequences in the 30 untranslated region (UTR) of specific mRNAs. For example, Nanos protein at the posterior of the Drosophila embryo directs posterior development, and this localization requires selective translation of posteriorly localized nanos mRNA. Spatial regulation of nanos translation requires Smaug protein bound to the nanos 30 UTR, which represses the translation of unlocalized nanos transcripts. While the function of 30 UTR-bound translational regulators is, in general, poorly understood, they presumably interact with the basic translation machinery. Here we demonstrate that Smaug interacts with the Cup protein and that Cup is an eIF4E-binding protein that blocks the binding of eIF4G to eIF4E. Cup mediates an indirect interaction between Smaug and eIF4E, and Smaug function in vivo requires Cup. Thus, Smaug represses translation via a Cup-dependent block in eIF4G recruitment.