FIGURE 8:

Model depicting IBTKα transcriptional and translational regulation during PERK induced eIF2α∼P. (A) During ER stress, the PERK arm of the UPR directs phosphorylation of eIF2α, resulting in global dampening of translation initiation. During this decrease in global mRNA translation, ATF4 and its downstream target IBTKα are suggested to be both transcriptionally induced and subject to preferential translation, which collectively can determine cell viability during ER stress. (B) The inhibitory uORFs 1 and 2 serve to repress IBTKα translational expression. uORF1 is a major inhibitory element, with uORF2 serving a secondary role. In response to ER stress, eIF2α∼P overcomes these inhibitory elements to translate the downstream IBTKα CDS.