Polymorphism Determines Effectiveness of Tumor-Suppressor Gene

Researchers have found that an amino acid polymorphism in the p53 protein coded by the TP53 tumor-suppressing gene determines how effectively the gene will be able to prevent cancer development. Their findings were published February 3, 2003, in the online edition of Nature Genetics.

"The existence of two variants, or polymorphisms, of p53 is not new, but we have discovered that the variant type in each cell can influence its tumor-suppressor ability,” explained senior author Dr. Maureen Murphy, a molecular biologist in the pharmacology department of Fox Chase Cancer Center (Philadelphia, PA, USA).

The normal role of p53 is to induce apoptosis in cells that would otherwise divide in an uncontrolled manner. While it has been known that variant forms of p53 existed with different abilities to suppress tumor growth, the basis for this variability was not known.

"People have one form or another of p53,” explained Dr. Murphy. "The p53 variant containing the amino acid called arginine is better at killing out-of-control cells. The other p53 variant with the amino acid proline is less capable of stopping errant cells.”

Data reported in the current study showed that at least one source of this enhanced apoptotic potential was the greater ability of the Arg72 variant to localize to the mitochondria. This localization was accompanied by release of cytochrome c into the cytosol. The authors suggest that p53 profiling could provide useful information on how best to tailor chemotherapy for treating individual patients.



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