Fig. 1.

Control of translation by eukaryotic initiation factor 2 (eIF2). eIF2 bound to GDP (eIF2-GDP) is recycled to the active eIF2-GTP by a reaction catalyzed by eIF2B. Once recycled, eIF2-GTP forms a ternary complex with initiator-methionine tRNA (Met-tRNAi) and 40S ribosome resulting in 43S pre-initiation complex. Four kinases activated by hemin deficiency/oxidative stress (HRI), viral infection (PKR), endoplasmic reticulum stress/hypoxia (PERK/PEK) and amino acid starvation/UV irradiation (GCN2); can phosphorylate eIF2 subunit α, stabilize eIF2-GDP–eIF2B complex (inactive) and prevents eIF2 recycling. These events result in a shut-off of the host protein synthesis and subsequently SG assembly (Fig. 2, i).