Activation of GCN2 in UV-irradiated cells inhibits translation.
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 alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) by activating the kinase GCN2 in a manner that does not require SAPK/JNK or p38 MAP kinase. GCN2-/- cells, and cells expressing nonphosphorylatable eIF2alpha as their only source of eIF2alpha 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.
Deng
Jing
J
Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec, Canada.
Harding
Heather P
HP
Raught
Brian
B
Gingras
Anne-Claude
AC
Berlanga
Juan Jose
JJ
Scheuner
Donalyn
D
Kaufman
Randal J
RJ
Ron
David
D
Sonenberg
Nahum
N
D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000528:radiation effects; D004789:Enzyme Activation; D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000528:radiation effects*; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D014466:Ultraviolet Rays
D011494:Protein Kinases; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases