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Genetic function discovered that could offer new avenue to cancer therapies
Date:2/3/2014

n of cancers."

But the activity and function of p53 can sometimes decline or fail, Leid said, and allow development of cancer. Promising approaches to cancer therapy are now based on activating or stimulating the p53 protein to do its job.

The new study has found that the Grasp gene is significantly involved in maintaining the proper function of p53. When "Grasp" is not being adequately expressed, the p53 protein that has entered the cell nucleus to either repair or destroy the cell comes back out of the nucleus before its work is finished.

"It appears that a primary function of Grasp is to form sort of a halo around the nucleus of a damaged skin cell, and act as kind of a plug to keep the p53 cell inside the nucleus until its work is done," Leid said. "A drug that could enhance Grasp function might also help enhance the p53 function, and give us a different way to keep this important tumor suppressor working the way that it is supposed to.

"This could be important," he said.

OSU experts created laboratory mice that lacked the Grasp gene, and so long as the mice were reared in a perfect environment, they developed normally. But when they were exposed to even a mild environmental stress ultraviolet light similar to moderate sun exposure they began to develop cellular abnormalities much more rapidly than ordinary mice. Most significantly, mutated skin cells did not die as they should have.

In normal mice, the same moderate light exposure caused a rapid increase in expression of the Grasp gene, allowing the p53 protein to stay in the nucleus and normal protective mechanisms to do their work.

Most current cancer therapies related to the p53 tumor suppression process are directed toward activating the p53 protein, Leid said. A therapy directed toward improving the Grasp gene function would be a different approach toward the same goal, he said, and might improve the efficacy of treatment.


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Contact: Mark Leid
mark.leid@oregonstate.edu
541-737-5809
Oregon State University
Source:Eurekalert

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