Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation
Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation
复制标题
DOI：
10.1038/sj.emboj.7600742
复制
发表时间：
2005-07-20
期刊：
影响因子：
11.4
通讯作者：
Kitajima, S
中科院分区：
文献类型：
--
作者：
Tamura, K;Hua, BY;Kitajima, S
c-myc原癌基因编码促进细胞周期进程和细胞增殖的转录因子，其缺陷导致严重的增殖速率减慢。ATF 3应激反应基因编码在应激条件下决定细胞命运中起作用的转录因子。然而，其在控制细胞增殖和其串扰调节中的生物学意义还没有很好地理解。在这里，我们报告的血清反应的ATF 3基因表达依赖于c-myc基因和c-Myc复合物在ATF/CREB位点的基因启动子起着介导的血清反应的作用。有趣的是，ATF 3的异位表达促进了c-myc缺陷细胞的增殖，主要是通过缓解这些细胞中观察到的G1期进展受阻，而ATF 3敲除显着抑制了野生型细胞的增殖。我们的研究表明，ATF 3是下游的c-Myc信号通路，并在介导的c-Myc的细胞增殖功能的作用。我们的研究结果提供了一个新的洞察应激反应基因ATF 3和原癌基因c-myc的功能联系。
The c-myc proto-oncogene encodes a transcription factor that promotes cell cycle progression and cell proliferation, and its deficiency results in severely retarded proliferation rates. The ATF3 stress response gene encodes a transcription factor that plays a role in determining cell fate under stress conditions. Its biological significance in the control of cell proliferation and its crosstalk regulation, however, are not well understood. Here, we report that the serum response of the ATF3 gene expression depends on c-myc gene and that the c-Myc complex at ATF/CREB site of the gene promoter plays a role in mediating the serum response. Intriguingly, ectopic expression of ATF3 promotes proliferation of c-myc-deficient cells, mostly by alleviating the impeded G1-phase progression observed in these cells, whereas ATF3 knockdown significantly suppresses proliferation of wild-type cells. Our study demonstrates that ATF3 is downstream of the c-Myc signaling pathway and plays a role in mediating the cell proliferation function of c-Myc. Our results provide a novel insight into the functional link of the stress response gene ATF3 and the protooncogene c-myc.