Mechanisms of p53-mediated apoptosis

The loss of p53-mediated apoptosis (programmed cell death) has been implica ted as an important event in tumour progression in a number of systems. p53 can induce or potentiate apoptosis through several mechanisms, both by reg ulating the expression of genes which can participate in the apoptotic resp onse and through transcriptionally independent means. There appears to be c ell type variability in both the response to p53 expression and in the requ irement for p53 transcriptional transactivation for the induction of apopto sis. It seems clear, however, that the induction of p53 in untransformed ce lls is more likely to result in cell-cycle arrest, whereas the expression o f p53 in their transformed counterparts is more likely to result in the ind uction of apoptosis, and this may, in part, reflect the deregulated express ion of E2F-1 in tumour cells. The synergistic action of p53 and E2F-1 in th e induction of apoptosis has raised the possibility that the reactivation o f p53 in transformed cells can be an effective tumour therapy.