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.
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 mammalianGCN2 as a mediator of the cellular response to UV stress.
Authors: Richa Tyagi; Neelam Shahani; Lindsay Gorgen; Max Ferretti; William Pryor; Po Yu Chen; Supriya Swarnkar; Paul F Worley; Katrin Karbstein; Solomon H Snyder; Srinivasa Subramaniam Journal: Cell Rep Date: 2015-02-07 Impact factor: 9.423
Authors: Francis Robert; Chris Williams; Yifei Yan; Elizabeth Donohue; Regina Cencic; Stephen K Burley; Jerry Pelletier Journal: Chem Biol Drug Des Date: 2009-07 Impact factor: 2.817