ATF4 mRNA is translated to yield ATF4 protein, which then transits to the nucleus (Blais et al. 2004, Ross et al. 2018). The mRNA of ATF4 contains 2 upstream ORFs (uORFs) (Ross et al. 2018 and inferred from the mouse homolog). The second uORF overlaps the ORF encoding ATF4 and thus prevents translation of ATF4. When EIF2S1 (eIF2-alpha) is phosphorylated, translation initiation is decreased overall, translation of the uORFs is suppressed, and translation of the ORF encoding ATF4 is increased (Blais et al. 2004, Ross et al. 2018, and inferred from mouse homologs).