Amorim Inês S, Lach Gilliard, Gkogkas Christos G
Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
The Patrick Wild Centre, The University of Edinburgh, Edinburgh, United Kingdom.
Front Genet. 2018 Nov 23;9:561. doi: 10.3389/fgene.2018.00561. eCollection 2018.
Protein synthesis in eukaryotic cells is a complex, multi-step and tightly regulated process. Translation initiation, the rate limiting step in protein synthesis, is dependent on the activity of eukaryotic translation Initiation Factor 4E (eIF4E). eIF4E is the cap-binding protein which, in synergy with proteins such as the helicase eIF4A and the scaffolding protein eIF4G, binds to mRNA, allowing the recruitment of ribosomes and translation initiation. The function of eIF4E is tightly regulated in cells under normal physiological conditions and can be controlled by post-translational modifications, such as phosphorylation, and by the binding of inhibitory proteins, including eIF4E binding proteins (4E-BPs) and CYFIP1. Recent studies have highlighted the importance of eIF4E in normal or aberrant function of the nervous system. In this mini-review, we will highlight the role of eIF4E function and regulation in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.
真核细胞中的蛋白质合成是一个复杂、多步骤且受到严格调控的过程。翻译起始是蛋白质合成中的限速步骤,它依赖于真核翻译起始因子4E(eIF4E)的活性。eIF4E是帽结合蛋白,它与解旋酶eIF4A和支架蛋白eIF4G等蛋白质协同作用,与mRNA结合,从而招募核糖体并启动翻译。在正常生理条件下,eIF4E的功能在细胞中受到严格调控,并且可以通过翻译后修饰(如磷酸化)以及抑制性蛋白的结合来控制,这些抑制性蛋白包括eIF4E结合蛋白(4E-BPs)和CYFIP1。最近的研究强调了eIF4E在神经系统正常或异常功能中的重要性。在本综述中,我们将重点介绍eIF4E功能和调控在神经发育和神经精神疾病病理生理学中的作用。