Abstract
Single mutations in the DNA binding domain of p53 cause a radical shift in function from tumor suppressor to oncogene. The mutated proteins lose the negative feedback regulation mediated by MDM2. Their oncogenic activity consists of a dominant negative inhibition of the remaining wild-type p53 protein, and a gain of function (GOF) activity independent of wild-type p53 inhibition. An understanding of the properties of these very common oncogenes is yielding promising therapeutic approaches, and is predicted to offer more clinical applications as the field develops.
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Sigal, A., Rotter, V. (2005). The Oncogenic Activity of p53 Mutants. In: Zambetti, G.P. (eds) The p53 Tumor Suppressor Pathway and Cancer. Protein Reviews, vol 2. Springer, Boston, MA. https://doi.org/10.1007/0-387-30127-5_9
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