Polager Shirley, Ginsberg Doron
The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan 52900, Israel.
Nat Rev Cancer. 2009 Oct;9(10):738-48. doi: 10.1038/nrc2718.
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.
在肿瘤发生过程中，细胞会发生突变，从而破坏控制增殖的正常机制。值得注意的是，在大多数（即便不是全部）人类肿瘤中，Rb-E2f和MDM2-p53通路均存在缺陷，这突出了这些通路在调节细胞周期进程和细胞活力方面的关键作用。对于这两条通路均失调这一现象的一种简单解释是，它们在细胞命运控制中独立发挥作用。然而，大量证据表明，除了对细胞命运的独立影响外，这两条通路之间还存在广泛的相互作用，尤其是转录因子E2F1和p53之间，这种相互作用会影响重要的细胞决策。本综述讨论了E2f和p53之间复杂相互作用的分子机制。
