文章：

打破循环：癌症中的E2F功能障碍

The broken cycle: E2F dysfunction in cancer

原文发布日期：2019-05-03

DOI: 10.1038/s41568-019-0143-7

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

细胞周期蛋白依赖性激酶（CDK）-RB-E2F轴构成了驱动细胞周期进程的核心转录机制，它决定了基因组复制的时间与保真度，并确保遗传物质在每次细胞分裂周期中准确传递。该轴的核心效应器是由八个不同E2F基因组成的转录激活因子和抑制因子家族。E2F转录活性通过转录与翻译调控、翻译后修饰、蛋白降解、共因子结合及亚细胞定位等方式在整个细胞周期中受到严格调控。该轴中一个或多个关键组分（CDK、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，会导致致癌性E2F活性增强，从而引发不受控的增殖。本文重点讨论非典型E2F家族新成员的特殊功能，阐述E2F蛋白的特异性与冗余功能，探讨E2F转录靶标异常表达如何促进癌症发展，并介绍当前及正在研发的靶向该致癌通路的治疗策略。

原文链接：

The broken cycle: E2F dysfunction in cancer