Is More p53 Better?

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Science  15 Nov 2002:
Vol. 298, Issue 5597, pp. 1301
DOI: 10.1126/science.298.5597.1301a

The p53 tumor suppressor protein has been dubbed the guardian of the genome because it prevents the proliferation of cells containing damaged DNA—cells that have the potential to become cancerous. Indeed, defects in p53 itself or in the pathways that activate it occur in the vast majority of human cancers.

To explore whether an extra copy of p53 might boost an organism's ability to defend against cancer, García-Cao et al. generated transgenic mice carrying a third copy of wild-type p53, the expression properties of which closely resembled those of the endogenous p53 alleles. These “super p53” mice not only showed enhanced activation of the p53-dependent response to DNA damage, but they developed significantly fewer tumors after exposure to chemical carcinogens. Interestingly, the “super p53” mice had a normal life-span, a finding that contrasts with results of an earlier study that had linked elevated p53 activity in mice to premature aging. Therapeutic up-regulation of p53 expression may help prevent cancer development. — PAK.

EMBO J., 21, 6225 (2002).

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