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Novel regulatory mechanism identified for key tumor suppressor p53

(PHILADELPHIA) Collaborating scientists from The Wistar Institute in Philadelphia and The Vienna Biocenter in Austria have identified a novel mechanism involved in normal repression of the p53 protein, perhaps the single most important molecule for the control of cancer in humans.

The new molecular pathway described in the study suggests intriguing approaches to diagnosing or intervening in the progression of many types of cancer. A report on the team's findings will be published online November 15 in the journal Nature.

"The p53 protein is vital for controlling cancer throughout the body," says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor at The Wistar Institute and senior author on the study. "The new mechanism we describe, driven by a previously unknown enzyme, represses the p53 protein when its activity is not needed.

"What we're looking at now is the possibility that this enzyme, if over-expressed or over-active, might interfere with p53's normal tumor suppressor function and perhaps cause cancer. If that's the case, then we could develop drugs to inhibit the enzyme that would have the effect of freeing p53 to do its job of suppressing cancer. Unusually high levels of the newly identified enzyme might also be useful as a diagnostic marker for cancer."

Responsible for tumor suppression throughout the body, the p53 protein has been found to be mutated and dysfunctional in more than half of human cancers. When working properly, p53 acts by binding to DNA to activate genes that direct cells with damaged DNA to cease dividing until the damage can be repaired. Cells with such damage include cancer cells, since all cancers track to genetic flaws of one kind or another, whether inherited or acquired. If repairs cannot be made, p53 commands the cells with damaged DNA to self-destruct so they are no longer a danger to the body.

This powerful ability of the p53 protein to shut down cell division and induce cell
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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
15-Nov-2006


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