EIF2AK3 and central nervous system cancer: UPR signalling has been shown to be required for sustained autophagy under hypoxia in colorectal carcinoma and glioma cells which were not able to maintain the LC3 levels required for autophagy under prolonged hypoxia when the ATF4-activating protein, PKR-Like ER Kinase (PERK) (Figure 1), was disrupted [29].