We went on to investigate the molecular mechanisms promoting this paradoxical IFN-ß synthesis in an otherwise translationally repressed environment. Induction of eIF2a phosphorylation by PERK during ER stress promotes rapid ATF4 synthesis and nuclear translocation, followed by the transcription of many downstream target genes important for the UPR [50] . Similarly, in presence of PKR, nuclear ATF4 levels were found to be upregulated in MEFs responding to cytosolic poly I:C, albeit less importantly than upon a bona fide UPR induced by thapsigargin ( Fig. 2A) .