A Killer Protein Starts Leaving Some Clues

A protein dubbed p53 is among the body's most intriguing substances. It normally helps repair DNA and prevents the unchecked growth of cells. But mutated versions--scientists have found more than 1,000--have been implicated in dozens of cancers. And now, a report in the July 15 Science shows that p53's normal action can even be blocked by viruses.

The development gf therapies for diseases caused when the protein goes awry has been hampered by lack of knowledge about how the molecule works. Part of the puzzle has been solved by researchers at New York's Memorial-Sloan Kettering Cancer Center. By shining X-rays onto crystallized p53 proteins, they determined the three-dimensional structure of a key region of the molecule. The results, reported in the same issue of Science, show that p53 binds to DNA's contours. This explains why mutations that change p53's shape prevent correct binding and thus block its normal action. Now the bad news: The molecule is so complex that many of the drugs being tested have no chance of working. This discovery, says Harvard University oncologist Stephen Friend in an accompanying commentary, "has set a higher hurdle."

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