Activation of GCN2 in UV-irradiated cells inhibits translation
Activation of GCN2 in UV-irradiated cells inhibits translation
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DOI：
10.1016/s0960-9822(02)01037-0
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发表时间：
2002-08-06
期刊：
影响因子：
9.2
通讯作者：
Sonenberg, N
中科院分区：
文献类型：
--
作者：
Deng, J;Harding, HP;Sonenberg, N
背景：哺乳动物细胞在紫外线照射下会抑制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被广泛研究，但对翻译抑制的机制知之甚少。结果：在这里，我们证明了紫外线照射通过激活激酶GCN2，以不需要SAPK/JNK或p38 MAP激酶的方式引发真核翻译起始因子2 (eIF2alpha) α亚基的磷酸化。GCN2-/-细胞和表达非磷酸化eIF2alpha作为eIF2alpha蛋白唯一来源的细胞，在紫外线照射下无法抑制翻译。结论：这些结果提供了紫外线照射对翻译抑制的机制，并确定了哺乳动物GCN2作为细胞对紫外线应激反应的介质的迄今未被认识的作用。
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.