Figure 2.

ERdj6 surveys the activation state of PERK. ERdj6 can adopt various subcellular localizations. Under control conditions, ERdj6 is located luminally and transfers BiP to PERK to keep PERK in a silenced state and to enable eIF2α-dependent RNA translation. In ER-stressed cells (as observed after 8 h thapsigargin treatment), ERdj6 is inserted in the ER membrane. Half of the membrane-anchored pool faces the lumen, and half of the pool faces the cytosol. Due to the increased demand of chaperoning activity, BiP dissociates from the luminal domain of PERK and enables the activation and autophosphorylation of PERK. The subsequent phosphorylation of eIF2α inhibits eIF2α-dependent translational processes. The translational arrest can be released by interaction of the cytosolic ERdj6 pool with the C-terminus of PERK (see text).