Slansky J E, Farnham P J
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.
Curr Top Microbiol Immunol. 1996;208:1-30. doi: 10.1007/978-3-642-79910-5_1.
E2F is a heterodimer composed of two partners, such as E2F1 and DP1. Although E2F1 can bind DNA as a homodimer and increase promoter activity, optimal DNA-binding and transcriptional activity occurs in the heterodimeric form. A model (Fig. 3) for the involvement of E2F activity in cell growth control that incorporates viral oncoproteins, positive regulators of cell growth (cyclins) and negative regulators of cell growth (tumor suppressor proteins) can now be advanced. Each aspect of this model is addressed in subsequent chapters of this book. It is likely that binding of growth-suppressing proteins, such as Rb, can inhibit the transactivation potential of E2F1, either by blocking the interaction of E2F1 with a separate component of the transcription complex or by bringing a repressor domain to the transcription complex (Flemington et al. 1993; Helin et al. 1993; Weintraub et al. 1992; Zamanian and La Thangue 1993; Zhu et al. 1993). Phosphorylation or sequestration of Rb by viral oncoproteins can free E2F. The influence of viral oncoproteins on E2F activity and the regulation of the different E2F complexes is the focus of the contributions by Cobrinik and by Cress and Nevens. The interaction of the free E2F induces a bend in the DNA that may also play a role in transactivation, perhaps by bringing proteins (such as an Sp1 or CCAAT family member) separated by distance on the promoter DNA into contact (Huber et al. 1994). Because E2F target genes encode proteins critical for cell growth, deregulation of E2F activity can have severe consequences, such as apoptosis or uncontrolled proliferation. The effect of altered expression of E2F activity on the cell cycle and on tumorigenicity is the focus of the contribution by Adams and Kaelin. Finally, a comparison of E2F to the genetically well-characterized factors that regulate G1/S phase transcription in yeast is the subject of the chapter by Breeden. This volume concludes with Farnham's summary of the rapid gains in knowledge concerning the E2F gene family that have been made in the past several years and provides a series of questions and lines of investigation that will be the focus of future studies.
E2F是一种由两个亚基组成的异源二聚体，比如E2F1和DP1。尽管E2F1能以同源二聚体形式结合DNA并增强启动子活性，但最佳的DNA结合和转录活性是以异源二聚体形式出现。现在可以提出一个关于E2F活性参与细胞生长调控的模型（图3），该模型纳入了病毒癌蛋白、细胞生长的正调控因子（细胞周期蛋白）和细胞生长的负调控因子（肿瘤抑制蛋白）。本书后续章节将探讨该模型的各个方面。生长抑制蛋白（如Rb）的结合可能会抑制E2F1的反式激活潜能，要么通过阻断E2F1与转录复合物中另一个组分的相互作用，要么通过将一个阻遏结构域带到转录复合物上（弗莱明顿等人，1993年；赫林等人，1993年；温特劳布等人，1992年；扎马尼亚和拉唐格，1993年；朱等人，1993年）。病毒癌蛋白对Rb的磷酸化或隔离作用可使E2F释放出来。病毒癌蛋白对E2F活性的影响以及不同E2F复合物的调控是科布林尼克、克雷斯和内文斯所做贡献的重点。游离E2F的相互作用会使DNA发生弯曲，这可能在反式激活中也发挥作用，或许是通过使在启动子DNA上被一段距离隔开的蛋白质（如一个Sp1或CCAAT家族成员）相互接触（胡贝尔等人，1994年）。由于E2F靶基因编码对细胞生长至关重要的蛋白质，E2F活性的失调可能会产生严重后果，如细胞凋亡或不受控制的增殖。E2F活性表达改变对细胞周期和肿瘤发生的影响是亚当斯和凯林所做贡献的重点。最后，布里登所著章节的主题是将E2F与在酵母中调控G1/S期转录的遗传特征明确的因子进行比较。本书最后是法纳姆对过去几年中关于E2F基因家族的知识迅速增长情况的总结，并提出了一系列问题和研究方向，这些将是未来研究的重点。
