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 the single greatest known selective advantage favoring cancer formation. Point mutations result not only in the loss of tumor suppressor functions, but also in the gain of tumor promotion functions. These dual circumstances may be unique to p53 and, in part, could explain the relatively powerful force behind this selection pressure. General mechanisms of gain of function by mutated p53 may include alteration in transcriptional modulation and newly acquired targets for transcriptional regulation and protein binding. Despite the direct significance of p53 mutations, loss of the remaining wild-type allele is usually required for 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.
Division of Medical Oncology, University of Texas Health Science Center at San Antonio 78284, USA.
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Elledge
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Lee
D000818:Animals; D016158:Genes, p53 / Q000502:physiology*; D015316:Genetic Therapy; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000628:therapy