Specifically, we recently demonstrated that Akt inactivation by genetic or pharmacological means induces eIF2αP via the activation of PERK and GCN2.33, 35 This is because PERK and GCN2 are inhibited by Akt-mediated phosphorylation and as such, each eIF2α kinase regains full activity under conditions of Akt inactivation.33, 35 This process may account for increased eIF2αP in tumor cells with impaired Akt S473 phosphorylation as indicated by mTORC2 disruption or pharmacological inhibition of Akt (Figures 6a and c). Here, EIF2AK3 is linked to neoplasm.