Ionizing radiation regulates expression of the c-jun protooncogene.

Ionizing radiation regulates expression of the c-jun protooncogene.
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DOI:
10.1073/pnas.87.15.5663
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发表时间:
1990-08
影响因子:
11.1
通讯作者:
M. Sherman;R. Datta;D. Hallahan;R. Weichselbaum;D. Kufe
M. Sherman;R. Datta;D. Hallahan;R. Weichselbaum;D. Kufe
中科院分区:
综合性期刊1区
文献类型:
--
作者:
M. Sherman;R. Datta;D. Hallahan;R. Weichselbaum;D. Kufe

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目前对电离辐射对基因表达的调控知之甚少。目前的研究表明,哺乳动物基因c-jun原癌基因在X射线的作用下被转录激活。C-jun基因编码AP-1蛋白复合体的一个组成部分,在参与各种细胞功能的早期信号事件中起重要作用。Northern印迹分析表明,电离辐射对c-jun基因转录水平的影响具有时间和剂量依赖性。转录连续分析表明,电离辐射刺激c-jun基因转录。此外,在没有蛋白质合成的情况下,c-jun RNA的半衰期延长。这些发现表明,辐射后c-jun RNA的增加受到转录和转录后机制的调节。此外,电离辐射对c-jun的诱导与剂量率反转效应有关,即降低剂量率会增加c-jun的表达。目前的结果同样表明,电离辐射增加了c-fos转录本的水平,以及Jun家族的另一个成员Jun-B的转录水平。综上所述,这些结果表明,早期反应基因的诱导在电离辐射的病理生理效应中发挥了作用。
There is little known about the regulation of gene expression by ionizing radiation exposure. The present studies demonstrate transcriptional activation of a mammalian gene, the c-jun protooncogene, by x-rays. The c-jun gene encodes a component of the AP-1 protein complex and is important in early signaling events involved in various cellular functions. The increase in c-jun transcripts by ionizing radiation was time- and dose-dependent as determined by Northern blot analysis. Transcriptional run-on analysis demonstrated that ionizing radiation stimulates the rate of c-jun gene transcription. Furthermore, the half-life of c-jun RNA was prolonged in the absence of protein synthesis. These findings indicate that the increase in c-jun RNA observed after irradiation is regulated by transcriptional and posttranscriptional mechanisms. Moreover, the induction of c-jun by ionizing radiation was associated with an inverse dose rate effect in that decreasing the dose rate resulted in increased c-jun expression. The present results similarly demonstrate that ionizing radiation increases levels of c-fos transcripts as well as that of jun-B, another member of the jun family. Taken together, these results suggest a role for induction of early response genes in the pathophysiologic effects of ionizing radiation.