Activation of GCN2 in UV-Irradiated Cells Inhibits Translation

• Published in: Current biology Vol. 12; no. 15; pp. 1279 - 1286
• Main Authors: Deng, Jing, Harding, Heather P., Raught, Brian, Gingras, Anne-Claude, Berlanga, Juan Jose, Scheuner, Donalyn, Kaufman, Randal J., Ron, David, Sonenberg, Nahum
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 06.08.2002
• Subjects: Animals; Cells, Cultured; DNA Replication - radiation effects; Enzyme Activation; Fibroblasts - physiology; Fibroblasts - radiation effects; JNK Mitogen-Activated Protein Kinases; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Protein Biosynthesis - radiation effects; Protein Kinases - deficiency; Protein Kinases - genetics; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases; Ultraviolet Rays
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/S0960-9822(02)01037-0

Background: Mammalian cells subjected to ultraviolet (UV) irradiation actively repress DNA replication, transcription, and mRNA translation. While the effects of UV irradiation on DNA replication and transcription have been extensively studied, the mechanism(s) responsible for translational repression are poorly understood. Results: Here, we demonstrate that UV irradiation elicits phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α) by activating the kinase GCN2 in a manner that does not require SAPK/JNK or p38 MAP kinase. GCN2−/− cells, and cells expressing nonphosphorylatable eIF2α as their only source of eIF2α protein, fail to repress translation in response to UV irradiation. Conclusions: These results provide a mechanism for translation inhibition by UV irradiation and identify a hitherto unrecognized role for mammalian GCN2 as a mediator of the cellular response to UV stress.