Figure 1.

Scheme of the PERK branch of the UPR. Unfolded proteins activate PERK, which phosphorylates eIF2α. This represses translation at the level of initiation. Some proteins, however, escape this repression and are preferentially translated after eIF2α phosphorylation, such as ATF4, which leads to the translation of the pro-apoptotic CHOP. Chronic translational repression leads to neurodegeneration in prion disease. Signaling through the integrated stress response (ISR) can also lead to eIF2α-P and translational repression. The sites of action of GSK2606414 and ISRIB are shown