Royzman I, Whittaker A J, Orr-Weaver T L
Department of Biology, Massachusetts Institute of Technology, and Whitehead Institute, Cambridge 02142, USA.
Genes Dev. 1997 Aug 1;11(15):1999-2011. doi: 10.1101/gad.11.15.1999.
The E2F transcription factor, a heterodimer of E2F and DP subunits, is capable of driving the G1-S transition of the cell cycle. However, mice in which the E2F-1 gene had been disrupted developed tumors, suggesting a negative role for E2F in controlling cell proliferation in some tissues. The consequences of disrupting the DP genes have not been reported. We screened for mutations that disrupt G1-S transcription late in Drosophila embryogenesis and identified five mutations in the dDP gene. Although mutations in dDP or dE2F nearly eliminate E2F-dependent G1-S transcription, S-phase still occurs. Cyclin E has been shown to be essential for S-phase in late embryogenesis, but in dDP and dE2F mutants the peaks of G1-S transcription of cyclin E are missing. Thus, greatly reduced levels of cyclin E transcript suffice for DNA replication until late in development. Both dDP and dE2F are necessary for viability, and mutations in the genes cause lethality at the late larval/pupal stage. The mutant phenotypes reveal that both genes promote progression of the cell cycle.
E2F转录因子是由E2F和DP亚基组成的异二聚体，能够驱动细胞周期的G1-S转换。然而，E2F-1基因被破坏的小鼠会发生肿瘤，这表明E2F在某些组织中对控制细胞增殖具有负向作用。破坏DP基因的后果尚未见报道。我们在果蝇胚胎发育后期筛选了破坏G1-S转录的突变，在dDP基因中鉴定出五个突变。尽管dDP或dE2F中的突变几乎消除了E2F依赖的G1-S转录，但S期仍会发生。细胞周期蛋白E已被证明在胚胎发育后期的S期是必需的，但在dDP和dE2F突变体中，细胞周期蛋白E的G1-S转录峰值缺失。因此，细胞周期蛋白E转录水平的大幅降低足以维持DNA复制直至发育后期。dDP和dE2F对生存能力都是必需的，基因中的突变会导致幼虫/蛹后期死亡。突变表型表明这两个基因都促进细胞周期的进程。
