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. 2020 Sep 1;12(9):2470. doi: 10.3390/cancers12092470

Figure 1.

Figure 1

Inhibition of translation pathways to induce the formation of SGs. (A) Active translation initiation complex (basal condition). Two pathways could be activated to induce translation inhibition upstream SGs formation. Under basal conditions, EIF2α is not phosphorylated and could allow the formation of the EIF2: tRNAiMet: GTP ternary complex of translation initiation. Additionally, MTOR is active and constitutively phosphorylates EIF4E-Binding Protein (4EBP). (B) The phosphorylation of a subunit of EIF2, EIF2α (or EIF2S1), by one (or more) kinase(s), notably HRI/EIF2AK1, PKR/EIF2AK2, PERK/EIF2AK3 and/or GCN2/EIF2AK4, prevents the hydrolyzed GDP from leaving the ternary complex EIF2α-tRNAmet-GTP by blocking the formation of an active complex with ATP necessary for translation initiation. (C) Hyper-phosphorylated 4EBP cannot interact with EIF4E, the mRNA cap-binding protein. However, induction of a stress response inactivates MTOR leading to a rapid de-phosphorylation of 4EBP, thereby allowing it to interact with EIF4E. The EIF4E: 4EBP interaction prevents EIF4E: EIF4G complex formation.