Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Nat Rev Cancer. 2019 Jun;19(6):326-338. doi: 10.1038/s41568-019-0143-7.
The cyclin-dependent kinase (CDK)-RB-E2F axis forms the core transcriptional machinery driving cell cycle progression, dictating the timing and fidelity of genome replication and ensuring genetic material is accurately passed through each cell division cycle. The ultimate effectors of this axis are members of a family of eight distinct E2F genes encoding transcriptional activators and repressors. E2F transcriptional activity is tightly regulated throughout the cell cycle via transcriptional and translational regulation, post-translational modifications, protein degradation, binding to cofactors and subcellular localization. Alterations in one or more key components of this axis (CDKs, cyclins, CDK inhibitors and the RB family of proteins) occur in virtually all cancers and result in heightened oncogenic E2F activity, leading to uncontrolled proliferation. In this Review, we discuss the activities of E2F proteins with an emphasis on the newest atypical E2F family members, the specific and redundant functions of E2F proteins, how misexpression of E2F transcriptional targets promotes cancer and both current and developing therapeutic strategies being used to target this oncogenic pathway.
细胞周期蛋白依赖性激酶 (CDK)-RB-E2F 轴形成了驱动细胞周期进程的核心转录机制，决定了基因组复制的时间和保真度，并确保遗传物质在每个细胞分裂周期中准确传递。该轴的最终效应物是编码转录激活因子和抑制因子的八个独特 E2F 基因家族的成员。E2F 转录活性通过转录和翻译调控、翻译后修饰、蛋白降解、与辅助因子结合和亚细胞定位在整个细胞周期中受到严格调控。该轴的一个或多个关键成分（CDKs、细胞周期蛋白、CDK 抑制剂和 RB 蛋白家族）的改变几乎存在于所有癌症中，并导致致癌性 E2F 活性增强，导致不受控制的增殖。在这篇综述中，我们讨论了 E2F 蛋白的活性，重点介绍了最新的非典型 E2F 家族成员、E2F 蛋白的特定和冗余功能、E2F 转录靶标的异常表达如何促进癌症以及当前和正在开发的用于靶向这种致癌途径的治疗策略。
