Deng Jing, Harding Heather P, Raught Brian, Gingras Anne-Claude, Berlanga Juan Jose, Scheuner Donalyn, Kaufman Randal J, Ron David, Sonenberg Nahum
Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec, Canada.
Curr Biol. 2002 Aug 6;12(15):1279-86. doi: 10.1016/s0960-9822(02)01037-0.
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.
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.
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.
受到紫外线（UV）照射的哺乳动物细胞会积极抑制DNA复制、转录和mRNA翻译。虽然紫外线照射对DNA复制和转录的影响已得到广泛研究，但导致翻译抑制的机制却知之甚少。
在此，我们证明紫外线照射通过激活激酶GCN2引发真核翻译起始因子2（eIF2α）的α亚基磷酸化，其激活方式不依赖于应激激活蛋白激酶/应激活化蛋白激酶（SAPK/JNK）或p38丝裂原活化蛋白激酶（p38 MAP激酶）。GCN2基因敲除细胞以及仅表达不可磷酸化的eIF2α作为其唯一eIF2α蛋白来源的细胞，在受到紫外线照射时无法抑制翻译。
这些结果为紫外线照射抑制翻译提供了一种机制，并确定了哺乳动物GCN2作为细胞对紫外线应激反应的介质这一此前未被认识到的作用。
