E2F-1-induced p53-independent apoptosis in transgenic mice
E2F-1-induced p53-independent apoptosis in transgenic mice
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DOI：
10.1038/sj.onc.1201915
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发表时间：
1998-07-16
期刊：
影响因子：
8
通讯作者：
Karlström, O
中科院分区：
文献类型：
--
作者：
Holmberg, C;Helin, K;Karlström, O
E2 F转录因子是视网膜母细胞瘤蛋白pRB的小桶靶标。通过E2 F的失活，PRE阻止进展到S期。为了测试E2 F的增殖功能，我们产生了表达人E2 F-1和/或人DP-1的转基因小鼠。当羟甲基戊二酰辅酶A还原酶启动子用于表达DP-1时，在多种组织中发生过表达，并且不赋予表型变化。与此相反，E2 F-1从相同的启动子的表达只在睾丸中获得，其中E2 F-1过表达引起萎缩和不育，通过一个过程，涉及在生殖上皮细胞凋亡增加。DP-1的同时过表达增强了这种作用。由于E2 F-1和DP-1过表达导致的睾丸萎缩与功能性p53无关，因为过表达E2 F-1和DP-1的p53缺失转基因小鼠也遭受睾丸萎缩。
The E2F transcription factors are keg targets for the retinoblastoma protein, pRB, By inactivation of E2Fs, PRE prevents progression to the S phase. To test proliferative functions of E2F, we generated transgenic mice expressing human E2F-1 and/or human DP-1. When the hydroxymethyl glutaryl coenzyme A reductase promoter was used to express DP-1, overexpression occurred in a variety of tissues and did not confer phenotypic changes. In contrast, expression of E2F-1 from the same promoter was obtained only in testicles, in which E2F-1 overexpression caused atrophy and sterility through a process involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered testicular atrophy.