biostudies-literatureUnknown19(9)Eytan KThe primary treatment for fatal pediatric-type diffuse high-grade glioma (PED-DHGG) which harbor the H3K27M or H3G34R/V mutation is radiation, but it provides only short-term relief. Inhibitors of phosphorylated eIF2α (PeIF2α) phosphatase-namely raphin-1 and salubrinal-decrease survival of PED-DHGG cell lines and sensitize them to radiation. However, although both drugs increase PeIF2α, they have different effects on common targets and different targets altogether. Here, we aimed to identify PeIF2α-phosphatase-dependent and PeIF2α-phosphatase-independent molecular targets. Raphin-1 but not salubrinal, decreased the level of BiP and CReP and increased that of DR5, in an ISRIB-independent manner. Raphin-1 induced similar changes in MEF^S51A cells and in irradiated PED-DHGG, suggestMolecular oncology2648-2669https://www.ebi.ac.uk/biostudies/studies/S-EPMC12420360biostudies-literatureRaphin-1 mediates the survival and sensitivity to radiation of pediatric-type diffuse high-grade glioma via phosphorylated eukaryotic initiation factor 2α-dependent and -independent processes.PMC12420360Eytan KLeitner MYalon MToren APaglin SfalseRaphin-1 mediates the survival and sensitivity to radiation of pediatric-type diffuse high-grade glioma via phosphorylated eukaryotic initiation factor 2α-dependent and -independent processes.The primary treatment for fatal pediatric-type diffuse high-grade glioma (PED-DHGG) which harbor the H3K27M or H3G34R/V mutation is radiation, but it provides only short-term relief. Inhibitors of phosphorylated eIF2α (PeIF2α) phosphatase-namely raphin-1 and salubrinal-decrease survival of PED-DHGG cell lines and sensitize them to radiation. However, although both drugs increase PeIF2α, they have different effects on common targets and different targets altogether. Here, we aimed to identify PeIF2α-phosphatase-dependent and PeIF2α-phosphatase-independent molecular targets. Raphin-1 but not salubrinal, decreased the level of BiP and CReP and increased that of DR5, in an ISRIB-independent manner. Raphin-1 induced similar changes in MEF^S51A cells and in irradiated PED-DHGG, suggest2025-01-01T00:00:00Z2025 Sep2026-04-20T03:15:13.012Z2026-04-20T03:10:13.169ZS-EPMC124203604063265910.1002/1878-0261.70081