Researchers have known for some time that the tumor-suppressor gene p53 plays a vital role in the body's struggle to stave off cancer. Exactly how p53 is activated in reponse to DNA damage, however, has remained a mystery. Now a study appearing today in the journal Science is finally shedding light on the matter. The new findings, scientists say, may one day lead to new cancer treatments.

The p53 gene monitors biochemical signals in cells that can indicate DNA damage or mutations. Upon detection of cancer development, p53 proteins build up in the cell's nucleus, instructing the cell to either halt the growth cycle or self-destruct. But under normal conditions, the cell does not need p53. In fact, the presence of p53 proteins in the nucleus would inhibit normal cell growth. The cell takes care of that "by exporting p53 from the nucleus to the cytoplasm for degradation," Yue Xiong of the University of North Carolina explains. Xiong and his team have found an amino acid sequence in the gene that controls this export. Apparently, when DNA damage occurs, a phosphate attaches to the p53 protein, preventing it from leaving the nucleus. As a result, the protein accumulates there, prompting the cell to act accordingly.

Looking forward, Xiong thinks the discovery could aid in developing cancer treatments. "In half of all tumor cells p53 is not working, sometimes because a kinase gene responsible for phosphorylation is mutated. When that gene is broken, DNA damage cannot be repaired because p53 is continually exported to the cytoplasm and getting degraded there," Xiong observes. "If we were to develop a compound to block p53 export, we might be able to restore p53 function in tumor cells with mutated kinase genes. We could give the compound to patients to wake up the p53 or prevent its degradation."