The preemptive quality control (pQC) pathway participates in the unfolded protein response regulating ER homeostasis, yet many components are not known. The role of p97 and its adaptor, AIRAPL, in proteasomal processing of pQC substrates is shown, and an insulin-processing mutant (R6C) is identified as a pQC substrate.

Background: Molecular mechanisms explaining stress-induced leaky scanning translation initiation regulation are poorly understood. Results: We demonstrate this relation and identify a post-translational modification on eIF1 that is stress responsive. Conclusion: Leaky scanning mediated by eIF1 phosphorylation is a stress-regulated process. Significance: Stress-induced global translation initiation can be regulated by means of leaky scanning as well as re-initiation.