p53: Gatekeeper, Caretaker Or Both?

Soon after the discovery of the p53 protein in 1979, the p53 gene was found to be mutated in about half of all human cancers. However, mainly due to the fact that the normally low levels of the p53 protein can be elevated in many cancers, it took some time to realise that p53 was in fact a tumour suppressor gene (Finlay et al., 1989; Levine et al., 1991). This concept was further consolidated by the discovery that the familial cancer predisposition known as Li-Fraumeni syndrome1 is linked to germ-line mutation of the p53 gene (for a review see Varley et al., 1997), and by the clear tumour propensity shown by p53 knock-out mice (for a review see Venkatachalam and Donehower, 1998).