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Jefferson scientists find guardian gene's choices crucial to stopping cancer process

(PHILADELPHIA) Scientists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have uncovered a novel pathway by which the anti-cancer gene p53 springs into action, protecting a damaged cell from becoming cancer. The gene can either halt the cell's growth or send it spiraling toward certain death. How this choice is made, the researchers say, could have implications for future strategies in chemotherapy drug development.

According to Steven McMahon, Ph.D., associate professor of cancer biology at Jefferson Medical College, who led the work, the p53 gene's or rather its protein's ability to direct a damaged cell to either stop growing or commit suicide depends on turning on separate groups of target genes. He and his co-workers have found that after a cell's DNA is damaged, the p53 protein's ability to bind to the DNA can be affected. Two enzymes, hMOF and TIP60, can chemically alter an amino acid, lysine 120, at the binding site, in turn influencing p53's decision on which target genes to turn on. The alteration can short-circuit p53's ability to cause the damaged cell to commit suicide, though it can still stop cell growth, suggesting that this change may help explain a mechanism behind p53's choice. They report their findings in the journal Molecular Cell.

"It's been known that p53 can induce cell cycle arrest or apoptosis (programmed cell death) as a way of eliminating developing cancer cells in response to cell damage, but no one has known how the choice is made," says Dr. McMahon. "This work narrows how the decision is made."

The findings could have implications for future drug development strategies. "Most chemotherapy strategies are aimed at getting cancer cells to die," Dr. McMahon says. "Figuring out what pathways p53 uses to cause that versus cell cycle arrest is important. It looks like this new modification that we have identified helps p53 make that decision."

"p53 is such an important
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
5-Jan-2007


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