The E2F pathway of growth control

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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, blocks 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.