The E2F pathway: new levels of control and regulation

癌症是由细胞异常生长和分裂引起的，通常被描述为细胞周期疾病。细胞周期是指一个细胞生长和分裂的过程，在正常的健康细胞中，这是一个受到严格调控的过程。细胞周期分为四个阶段，其中一个主要的控制点是细胞从最初的G1期进入S期，这是细胞开始合成和复制DNA为细胞分裂做准备的时候。在哺乳动物细胞中，E2F是一种至关重要的控制蛋白，因为它决定细胞是否进入S期。E2F的活性受到一些关键蛋白的调控，这些蛋白起着“制动”作用。包括视网膜母细胞瘤肿瘤抑制蛋白（pRb），它通过与E2F形成蛋白质复合物，阻断E2F的活性。最重要的是，在人类肿瘤细胞中，pRb通常是不活跃的，这意味着通常受到严格调控的E2F活性被释放出来，提供一个永久的信号，驱使细胞无限制地生长和分裂。这里描述的研究计划想要剖析不同类型的E2F活性的作用和调节，并评估其对正常细胞和肿瘤细胞生长的贡献。由于癌症中E2F的异常控制，本研究可能会发现新的治疗机会，以防止肿瘤细胞的生长。

Cancer results from abnormal cell growth and division, and is frequently described as a disease of the cell cycle. The cell cycle refers to the process through which one cell grows and divides which, in normal healthy cells, is a tightly regulated process. The cell cycle is divided into four phases, where a major point of control exists as cells progress from the initial G1 phase into S phase, which is when cells begin to synthesise and copy their DNA in preparation for cell division. In mammalian cells, E2F is a control protein of central importance because it governs whether cells do or do not enter S phase. The activity of E2F is regulated by a number of key proteins that act as a ?braking? system, and includes the retinoblastoma tumour suppressor protein (pRb) which, by forming a protein complex with E2F, block E2F activity. Most importantly, in human tumour cells pRb is usually inactive, which means that the normally tightly regulated E2F activity is unleashed, providing a permanent signal that drives cells into unrestrained growth and division. The programme of study described here wants to dissect the role and regulation of different types of E2F activity, and assess the contribution to normal and tumour cell growth. Because of the abnormal control of E2F in cancer, this study is likely to identify new therapeutic opportunities for preventing the growth of tumour cells.