Discovery of a missing link in the p53 gene may lead to improved cancer treatment

In a study recently published in Genes and Development, scientists from Singapore and the University of Dundee employed a "genetic trick" to turn zebrafish, which carry the same p53 gene as humans, green when the p53 gene was switched on. This allowed the scientists to explore how the gene, which blocks the development of tumors and stops them from dividing when repair work is being done, is regulated. In 50 percent of all cancers, the p53 gene is either damaged or inactive, enabling those cells to continue dividing and forming cancer.

As they discovered, the gene not only manufactures the p53 protein, but it also makes an alternative "control switch" variation of the protein, which is known as an isoform. They learned that without the isoform switch, zebrafish, which can normally survive low doses of radiation, died after exposure. The gene was unable to repair the damage, which, according to the scientists, proves that the isoform switch is instrumental in enabling p53 to carry out its repair work.

"The function of p53 is critical to the way that many cancer treatments kill cells since radiotherapy and chemotherapy act in part by triggering cell suicide in response to DNA damage," says Lead Researcher Professor Sir David Lane. "So understanding more about how this gene is controlled in cells is really important in finding ways to prevent cells from turning cancerous." And adds Lesley Walker, Director of Cancer Information for Cancer Research UK, "This is a really exciting study which improves our understanding of how the p53 gene works. Discovering how it is regulated will have incredibly important implications in the development of better drugs and ways to diagnose cancer."