Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada.
Arcalis, Inc., Kashiwa 277-0871, Japan.
Genes (Basel). 2023 Nov 14;14(11):2076. doi: 10.3390/genes14112076.
Translation initiation in eukaryotes is regulated at several steps, one of which involves the availability of the cap binding protein to participate in cap-dependent protein synthesis. Binding of eIF4E to translational repressors (eIF4E-binding proteins [4E-BPs]) suppresses translation and is used by cells to link extra- and intracellular cues to protein synthetic rates. The best studied of these interactions involves repression of translation by 4E-BP1 upon inhibition of the PI3K/mTOR signaling pathway. Herein, we characterize a novel 4E-BP, C8ORF88, whose expression is predominantly restricted to early spermatids. C8ORF88:eIF4E interaction is dependent on the canonical eIF4E binding motif (4E-BM) present in other 4E-BPs. Whereas 4E-BP1:eIF4E interaction is dependent on the phosphorylation of 4E-BP1, these sites are not conserved in C8ORF88 indicating a different mode of regulation.
真核生物的翻译起始在几个步骤中受到调节,其中之一涉及帽结合蛋白的可用性以参与帽依赖性蛋白合成。eIF4E 与翻译抑制剂(eIF4E 结合蛋白 [4E-BPs])结合抑制翻译,细胞利用它将细胞外和细胞内的信号与蛋白质合成速率联系起来。这些相互作用中研究最多的是在抑制 PI3K/mTOR 信号通路时,由 4E-BP1 抑制翻译。在此,我们描述了一种新型的 4E-BP,C8ORF88,其表达主要局限于早期精母细胞。C8ORF88:eIF4E 相互作用依赖于其他 4E-BPs 中存在的典型 eIF4E 结合基序 (4E-BM)。虽然 4E-BP1:eIF4E 相互作用依赖于 4E-BP1 的磷酸化,但这些位点在 C8ORF88 中并不保守,表明存在不同的调节模式。