Figure 1.

eIF2α is a control nexus integrating diverse stimuli to regulate translation. The eukaryotic initiation factor 2 (eIF2) is required for the formation of the ternary complex [consisting of eIF2 (α, β, and γ subunits), Met-tRNA_i, and GTP] whose role is to deliver the initiator Met-tRNA_i to the P site of the 40S ribosomal subunit, enabling translation initiation. eIF2 exists in two distinct configurations – the GDP bound (inactive) and GTP bound (active), but only the GTP-bound form can bind Met-tRNA_i. In response to diverse stress stimuli, distinct protein kinases phosphorylate the α subunit of eIF2 at serine 51, ultimately locking eIF2 in an inactive eIF2 complex with eIF2B. As a result, availability of the ternary complex significantly declines ultimately resulting in the inhibition of translation globally. Selective translation of a subset of mRNAs with uORFs continues, however, allowing cells to express proteins required for adaptation to stress conditions.