Duronio R J, Brook A, Dyson N, O'Farrell P H
Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA.
Genes Dev. 1996 Oct 1;10(19):2505-13. doi: 10.1101/gad.10.19.2505.
Both the heterodimeric transcription factor, E2F, and the G1 cyclin, cyclin E, are required for the G1-S transition at the start of the metazoan cell cycle. It has been established that cyclin E can act as an upstream activator of E2F. In addition to this action, we show here that cyclin E has an essential role in DNA replication distinct from activating E2F. We have created transgenic Drosophila capable of inducible, ectopic production of E2F activity. Simultaneous overexpression of both Drosophila E2F subunits, dE2F and dDP, in embryos stimulated the expression of multiple E2F-target genes including cyclin E, and also caused the initiation of S phase. Mutation of cyclin E prevented the initiation of S phase after overexpression of dE2F/dDP without affecting induction of target gene expression. Thus, E2F-directed transcription cannot bypass loss of cyclin E in Drosophila embryos.
异源二聚体转录因子E2F和G1期细胞周期蛋白E（cyclin E）都是后生动物细胞周期开始时G1期向S期转变所必需的。已经确定，细胞周期蛋白E可以作为E2F的上游激活剂。除了这一作用外，我们在此表明，细胞周期蛋白E在DNA复制中具有不同于激活E2F的重要作用。我们构建了能够诱导异位产生E2F活性的转基因果蝇。在胚胎中同时过表达果蝇E2F的两个亚基dE2F和dDP，刺激了包括细胞周期蛋白E在内的多个E2F靶基因的表达，还引发了S期的起始。细胞周期蛋白E的突变阻止了dE2F/dDP过表达后S期的起始，而不影响靶基因表达的诱导。因此，在果蝇胚胎中，E2F介导的转录不能绕过细胞周期蛋白E的缺失。
