New Cousin to Cell Security Guard

Scientists have identified the first gene with a strong resemblance to the p53 gene, an important tumor suppressor linked to almost half of all human cancers. Researchers hope that the new gene, described in tomorrow's issue of Cell, will give them a better understanding of the origins of many common cancers.

Geneticist Daniel Caput and his colleagues at the pharmaceutical company Sanofi Recherche in Labege, France, happened on the new gene while searching for cellular receptors of the immune system. When the French team checked one gene that came up in the search, they were shocked to find that its sequence was reminiscent of p53, a cellular "security guard" that stops cell division when DNA has been damaged and allows the cell to make repairs. They then contacted their longtime collaborator Frank McKeon, who studies gene expression and cell division at Harvard Medical School in Boston.

On closer inspection, the team found striking parallels between p53 and the new protein, called p73. One section of p73 closely resembles the so-called "core binding region" where p53 attaches itself to DNA. Equally intriguing, the p73 gene resides in a region of chromosome 1, thought to harbor multiple unidentified tumor suppressor genes. (This region is lost in about half of childhood nervous system cancers called neuroblastomas, as well as in some melanomas and in some carcinomas of the breast and colon.)

But key evidence of tumor suppression is still lacking. When checked, several neuroblastoma cell lines did not have mutations of p73 that would lead to rampant cell growth. Until such mutations are found, or someone finds an inherited mutation in the gene in persons with some form of hereditary cancer, it is "still up for grabs" whether p73 is a tumor suppressor, says cancer geneticist Bert Vogelstein of Johns Hopkins University School of Medicine.