Schulze A, Zerfass K, Spitkovsky D, Middendorp S, Bergès J, Helin K, Jansen-Dürr P, Henglein B
Deutsches Krebsforschungszentrum, Forschungsschwerpunkt Angewandte Tumorvirologie, Abteilung 620, Heidelberg, Germany.
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11264-8. doi: 10.1073/pnas.92.24.11264.
Cyclin A is involved in the control of S phase and mitosis in mammalian cells. Expression of the cyclin A gene in nontransformed cells is characterized by repression of its promoter during the G1 phase of the cell cycle and its induction at S-phase entry. We show that this mode of regulation is mediated by the transcription factor E2F, which binds to a specific site in the cyclin A promoter. It differs from the prototype E2F site in nucleotide sequence and protein binding; it is bound by E2F complexes containing cyclin E and p107 but not pRB. Ectopic expression of cyclin D1 triggers premature activation of the cyclin A promoter by E2F, and this effect is blocked by the tumor suppressor protein p16INK4.
细胞周期蛋白A参与哺乳动物细胞S期和有丝分裂的调控。在未转化细胞中，细胞周期蛋白A基因的表达特征是在细胞周期的G1期其启动子受到抑制，而在进入S期时被诱导。我们发现这种调控模式是由转录因子E2F介导的，E2F与细胞周期蛋白A启动子中的一个特定位点结合。它在核苷酸序列和蛋白质结合方面与原型E2F位点不同；它被含有细胞周期蛋白E和p107但不含有pRB的E2F复合物所结合。细胞周期蛋白D1的异位表达会触发E2F对细胞周期蛋白A启动子的过早激活，而这种效应被肿瘤抑制蛋白p16INK4所阻断。
