Figure 1. Model of how EIF2AK3/PERK-mediated autophagy promotes tumorigenesis by MYC. A hyperactive MYC increases protein synthesis and leads to accumulation of unfolded proteins in the ER, which activates the ER kinase EIF2AK3/PERK. EIF2AK3/PERK in turn phosphorylates EIF2S1/eIF2α, leading to attenuation of global protein synthesis. Conversely, phosphorylated EIF2S1/eIF2α promotes preferential translation of the transcription factor ATF4, which induces cytoprotective autophagy. Therefore, EIF2AK3/PERK-mediated reduction of protein synthesis, selective translation of certain mRNAs and induction of autophagy, work together to block cancer cell death.