LIFE AND DEATH BY P53

p53 is a multifunctional protein which plays a role in modulating gene transcription, policing cell cycle checkpoints, activating apoptosis, controlling DNA replication and repair, maintaining genomic stability and responding to genetic insults. Mutation of the p53 gene confers t he single greatest known selective advantage favoring cancer formation . Point mutations result not only in the loss of tumor suppressor func tions, but also in the gain of tumor promotion functions. These dual c ircumstances may be unique to p53 and, in part, could explain the rela tively powerful force behind this selection pressure. General mechanis ms of gain of function by mutated p53 may include alteration in transc riptional modulation and newly acquired targets for transcriptional re gulation and protein binding, Despite the direct significance of p53 m utations, loss of the remaining wild-type allele is usually required f or the formation of tumors in the natural setting. Novel applications of the basic scientific knowledge of p53 could lead to an improvement in cancer treatment, hopefully in the not so distant future.