Phosphorylation of eukaryotic translation initiation factor 4E is critical for growth
Phosphorylation of eukaryotic translation initiation factor 4E is critical for growth
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DOI：
10.1128/mcb.22.6.1656-1663.2002
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发表时间：
2002-03-01
影响因子：
5.3
通讯作者：
Lasko, P
中科院分区：
文献类型：
--
作者：
Lachance, PED;Miron, M;Lasko, P
真核生物翻译起始因子4E （eIF4E）结合在mrna 5'末端的帽状结构上，是控制蛋白质合成的关键靶点。在许多系统中，eIF4E在响应细胞外刺激时被磷酸化，但迄今为止，生物化学证据对这种修饰的生物学意义一直模棱两可。这里我们用遗传方法来解决这个问题。我们发现，在黑腹果蝇中，纯合子eIF4E突变体在幼虫发育过程中抑制生长。在果蝇eIF4EI中，Ser251对应于哺乳动物eIF4E的Ser209，后者在响应细胞外信号时被磷酸化。我们发现，在体内，eIF4EI Ser251突变体不能结合标记的磷酸盐。此外，在eIF4E突变背景下表达eIF4E（Ser251Ala）的转基因果蝇生物的生存能力降低。逃脱者比对照组的兄弟姐妹发育得更慢，体型也更小。这些遗传数据提供了证据，证明eIF4E磷酸化具有重要的生物学意义，对正常生长发育至关重要。
Eukaryotic translation initiation factor 4E (eIF4E) binds to the cap structure at the 5' end of mRNAs and is a critical target for the control of protein synthesis. eIF4E is phosphorylated in many systems in response to extracellular stimuli, but biochemical evidence to date has been equivocal as to the biological significance of this modification. Here we use a genetic approach to this problem. We show that, in Drosophila melanogaster, homozygous eIF4E mutants arrest growth during larval development. In Drosophila eIF4EI, Ser251 corresponds to Ser209 of mammalian eIF4E, which is phosphorylated in response to extracellular signals. We find that, in vivo, eIF4EI Ser251 mutants cannot incorporate labeled phosphate. Furthermore, transgenic Drosophila organisms expressing eIF4E(Ser251Ala) in an eIF4E mutant background have reduced viability. Escapers develop more slowly than control siblings and are smaller. These genetic data provide evidence that eIF4E phosphorylation is biologically significant and is essential for normal growth and development.