(PHILADELPHIA) So vital is the p53 tumor suppressor gene in controlling cancer that its dysfunction is linked to more than half of human cancers. At the same time, the genes capacity for shutting down cell growth, even causing cells to commit suicide if necessary, is so absolute that it must be tightly regulated to maintain the optimal balance between protecting against cancer and permitting normal growth.
Now, a study by scientists at The Wistar Institute reveals new levels of subtlety in the bodys management of this all-important tumor suppressor gene and the protein it produces. The experiments show that, while the addition of a specific molecule at a particular site on the p53 protein prevents it from acting, the addition of a second copy of the same molecule at the same site reverses the effect, sending p53 into action. Further, removal of the second copy returns the protein to its repressed state.
In addition to the implications for understanding the activity of the p53 gene, the findings also outline an important new cycle of gene-regulating modifications involving the addition and removal of the molecules, called methyl groups, that may be widespread in the genome. A report on the study appears in the September 6 issue of Nature.
The p53 tumor suppressor is extremely potent in halting cell growth, says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor at The Wistar Institute and senior author on the study. So, as critical as p53 is in protecting against the unchecked growth of cancer, you dont want it constantly on. If it were always on, your cells wouldnt be able to grow normally. Yet it needs to be constantly on call for activation against cancer and other aberrant cellular developments. Our study shows one way that the cell, working at one particular location on the p53 protein, maintains a nuanced but firm control over the genes activity.
Responsible for tumor suppression throughout the body, the p53 gene
|Contact: Franklin Hoke|
The Wistar Institute