eIF2的翻译抑制作用

帮助将抑制因子tRNA交付到核糖体的翻译因子eIF2利用GTP水解的能量来发挥功能。另一个因子eIF5已知在当eIF2与抑制因子tRNA和核糖体结合时会加快eIF2的GTP酶活性。在这项研究中，研究人员确定了eIF5的另外两个作用。

一个涉及在eIF2上稳定GDP（GTP水解的产物）；另一个涉及其通过磷酸化的eIF2来发挥作用、以抑制鸟甙酸交换因子eIF2B。这些结果澄清了我们对翻译抑制怎样被调控的认识。 

eIF5 has GDI activity necessary for translational control by eIF2 phosphorylationMartin D. Jennings & Graham D. Pavitt

Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK【Abstract】In protein synthesis initiation, the eukaryotic translation initiation factor (eIF) 2 (a G protein) functions in its GTP-bound state to deliver initiator methionyl-tRNA (tRNAiMet) to the small ribosomal subunit and is necessary for protein synthesis in all cells1, 2. Phosphorylation of eIF2 [eIF2(αP)] is critical for translational control in diverse settings including nutrient deprivation, viral infection and memory formation3, 4, 5. eIF5 functions in start site selection as a GTPase accelerating protein (GAP) for the eIF2·GTP·tRNAiMet ternary complex within the ribosome-bound pre-initiation complex6, 7, 8. Here we define new regulatory functions of eIF5 in the recycling of eIF2 from its inactive eIF2·GDP state between successive rounds of translation initiation. First we show that eIF5 stabilizes the binding of GDP to eIF2 and is therefore a bi-functional protein that acts as a GDP dissociation inhibitor (GDI). We find that this activity is independent of the GAP function and identify conserved residues within eIF5 that are necessary for this role. Second we show that eIF5 is a critical component of the eIF2(αP) regulatory complex that inhibits the activity of the guanine-nucleotide exchange factor (GEF) eIF2B. Together our studies define a new step in the translation initiation pathway, one that is critical for normal translational controls.