Caspase-dependent apoptosis by ectopic expression of E2F-4
Caspase-dependent apoptosis by ectopic expression of E2F-4
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DOI：
10.1038/sj.onc.1203833
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发表时间：
2000-09-28
期刊：
影响因子：
8
通讯作者：
Magae, J
中科院分区：
文献类型：
--
作者：
Chang, YC;Nakajima, H;Magae, J
E2F是调控哺乳动物细胞周期和凋亡的转录因子家族。E2F-1-3定位于细胞核内，优先结合pRb，而E2F-4和5没有核定位信号，优先结合p107/p130。E2F-6抑制其他E2F蛋白的转录活性。DP-1和dp - 2是每个E2F蛋白的异二聚体伴侣。利用四环素响应启动子，我们比较了E2F-1、DP-I和E2F-4异位表达对中国仓鼠细胞系细胞周期进程和凋亡的影响。我们发现E2F-4以及DP-I和E2F-1诱导生长停滞和caspase依赖性凋亡，E2F-4对细胞周期进程无明显影响，而E2F-1诱导静止细胞和DP-1阻滞细胞在G1期的DNA合成；E2F-4的异位表达不激活e2f依赖性转录。我们的研究结果表明，E2F-4的高水平表达通过不同于E2F-1和DP-1的机制诱导哺乳动物细胞的生长停滞和凋亡。
E2F is a family of transcription factors which regulates cell cycle and apoptosis of mammalian cells. E2F-1-3 localize in the nucleus, and preferentially bind pRb, while E2F-4 and 5 have no nuclear localization signal and preferentially bind p107/p130. E2F-6 suppresses the transcriptional activity of other E2F proteins. DP-1 and 2 are heterodimeric partners of each E2F protein. Using tetracycline-responsive promoters, here we compared the effects of ectopic expression of E2F-1, DP-I and E2F-4 on cell cycle progression and apoptosis in Chinese hamster cell lines, We found that E2F-4, as well as DP-I and E2F-1, induced growth arrest and caspase-dependent apoptosis, E2F-4 did not have a marked effect on cell cycle progression, while E2P-1 induced DNA synthesis of resting cells and DP-1 arrested cells in G1, Ectopic expression of E2F-4 did not activate E2F-dependent transcription. Our results suggest that expression of E2F-4 at elevated levels induces growth arrest and apoptosis of mammalian cells through a mechanism distinct from E2F-1 and DP-1.