Drug discovery and p53

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In this article David Lane and Ted Hupp discuss the p53 gene. The p53 gene is one of many tumour suppressors and appears to be relatively unique in its function at a nodal point as a mediator of the cellular response to changes in the microenvironment. In this article the authors outline the p53 transcriptional pathway, mutant p53 as an anti-cancer drug target and refolding of the structural class of mutant p53.

Molecular characterization of the p53 protein has shown that its conformational flexibility and intrinsic thermodynamic instability provide a foundation from which its conformation can be quickly post-translationally modified. The evolution of the transformed cell involves the sequential mutation in oncogenes and tumour suppressor genes that gives selective growth advantage to populations of cells, thus leading to clonal outgrowth of the tumour.

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