文章：

p53和E2f：生死攸关的伙伴

p53 and E2f: partners in life and death

原文发布日期：2009-10-01

DOI: 10.1038/nrc2718

类型: Review Article

开放获取: 否

要点：

1. There is extensive crosstalk between the Rb–E2f and MDM2–p53 pathways, and specifically between the transcription factors E2F1 and p53, which influences vital cellular decisions.
2. The abundance and activity of both p53 and E2f are often controlled by the same cancer-associated stimuli. Their common regulators include checkpoint kinases and acetyltransferases, MDM2 and the CDKN2A locus.
3. Deregulated E2f, which is often present in human tumours, constitutes an oncogenic stress that activates p53. Specifically, E2f indirectly affects the level and activity of p53 by upregulating the expression of many proteins that stabilize and activate p53. Examples include ARF, ataxia telangiectasia mutated and PIN1.
4. E2f and p53 cooperate in restricting tumorigenesis by inducing cell death. Their cooperation in apoptosis is attributed to the ability of E2F1 to activate p53. In addition, they activate many pro-apoptotic genes that may cooperate in apoptosis.
5. Protein complexes that contain Rb family members and repressor E2fs mediate p53-induced growth arrest and senescence; the latter is an important in vivo mechanism that contributes to protection against cancer.

要点翻译：

1. Rb–E2f与MDM2–p53通路之间存在广泛的交互对话，尤其是在转录因子E2F1与p53之间，这种相互作用直接影响细胞的重要命运决策。
2. p53和E2f的丰度与活性常受相同癌症相关刺激因子的调控。它们的共同调节因子包括检查点激酶、乙酰转移酶、MDM2以及CDKN2A基因座。
3. 人类肿瘤中常见的E2f失调会构成致癌应激从而激活p53。具体而言，E2f通过上调多种能稳定并激活p53的蛋白质表达（如ARF、共济失调毛细血管扩张突变基因和PIN1），间接影响p53的水平与活性。
4. E2f与p53通过诱导细胞死亡协同抑制肿瘤发生。两者在凋亡中的协同作用归因于E2F1激活p53的能力。此外，它们还能激活多个促凋亡基因，这些基因可能在凋亡过程中产生协同效应。
5. 含Rb家族成员和抑制性E2f的蛋白复合物介导p53诱导的生长停滞与衰老，其中衰老是体内抗肿瘤保护机制的重要环节。

英文摘要：

During tumour development cells sustain mutations that disrupt normal mechanisms controlling proliferation. Remarkably, the Rb–E2f and MDM2–p53 pathways are both defective in most, if not all, human tumours, which underscores the crucial role of these pathways in regulating cell cycle progression and viability. A simple interpretation of the observation that both pathways are deregulated is that they function independently in the control of cell fate. However, a large body of evidence indicates that, in addition to their independent effects on cell fate, there is extensive crosstalk between these two pathways, and specifically between the transcription factors E2F1 and p53, which influences vital cellular decisions. This Review discusses the molecular mechanisms that underlie the intricate interactions between E2f and p53.

摘要翻译： 

在肿瘤发展过程中，细胞会获得一些突变，这些突变会破坏控制增殖的正常机制。值得注意的是，Rb–E2f和MDM2–p53这两条通路在大多数（如果不是全部）人类肿瘤中都存在缺陷，这凸显了它们在调节细胞周期进程和细胞存活中的关键作用。一个对这些通路同时失调的简单解释是，它们在细胞命运控制中独立发挥作用。然而，大量证据表明，除了它们对细胞命运的独立影响外，这两条通路之间，特别是转录因子E2F1和p53之间，存在广泛的交互作用，这种交互作用影响着细胞的重大决策。本综述探讨了E2f与p53之间复杂相互作用的分子机制。

原文链接：

p53 and E2f: partners in life and death