GALVESTON, September 16, 2011 Researchers have shown for the first time that the protein fortilin promotes growth of cancer cells by binding to and rendering inert protein p53, a known tumor suppressor. This finding by researchers at the University of Texas Medical Branch may lead to treatments for a range of cancers and atherosclerosis, which p53 also helps prevent, and appears in the current print issue of the Journal of Biological Chemistry.
"The p53 protein is a critical defense against cancer because it activates genes that induce apoptosis, or the death of cells. However, p53 can be made powerless by mutations and inhibitors like fortilin," said Dr. Ken Fujise, lead author of the study and director, Division of Cardiology at UTMB.
Fortilin, an amino acid polypeptide protein, works in direct opposition to p53, protecting cells from apoptosis. Fujise discovered fortilin in 2000 and the protein has become a central focus of his research. This study marks the first time that scientists have been able to show the exact mechanism whereby fortilin exerts its anti-apoptotic activity.
Fujise and his team used cell cultures and animal models to show that fortilin binds to and inhibits p53, preventing it from activating genes, such as BAX and Noxa, that facilitate cell death. Thus, cells that would be killed are allowed to proliferate.
"When normal cells become cancer cells, our bodies' natural biological response is to activate p53, which eliminates the hopelessly damaged cells," said Fujise. "This process explains why the majority of people are able to stay cancer-free for most of their lives. Conversely, mutated p53 genes are seen in more than half of all human cancers, making them the most frequently observed genetic abnormality in cancer."
According to Fujise, upon further research and validation of the biological mechanism described in this study, scientists can begin exploring compounds that could modulate
|Contact: Jim Kelly|
University of Texas Medical Branch at Galveston