Figure 2: Global translation inhibition by eIF2α phosphorylation. Several stress stimuli activate distinct protein kinases, which in turn phosphorylate eIF2α. The phosphorylation of eIF2α enhances the affinity of eIF2-complex (α, β, and γ subunits) for eIF2B. This renders eIF2-complex inactive for the initiator tRNA delivery to the ribosome. However, a subset of mRNAs harboring cis-elements such as internal ribosome entry site (IRES) or upstream open reading frames (uORFs) are preferentially translated during eIF2α phosphorylation conditions. These mechanisms allow production of stress-related proteins. GCN2: general control nonderepressible-2; PKR: protein kinase R; HRI: heme-regulated inhibitor kinase; PERK: PKR-like endoplasmic reticulum kinase.