Protein Protects Cells from Cancer with 1-2-3 Punch: Scientists Find Third Strategy for Tumor Suppressor P53
Saey, Tina Hesman, Science News
Cells, do you need layers of cancer protection but hate juggling multiple proteins? Then an important tumor suppressor is for you. This cancer-controlling protein, p53, does not one, not two, but three different jobs, all in one convenient package, a new study shows.
Previous studies have demonstrated that p53 stops cancer from developing by sensing stress, such as DNA damage, and turning on genes that prevent cells from dividing. The protein, which is a normal component of cells, also teams up with other molecules to trigger apoptosis, a type of cellular suicide, in over-stressed cells.
Now, researchers from the University of Tokyo and colleagues report in the July 23 Nature that p53 helps slice RNA into small regulatory molecules called microRNAs. These microRNAs help control production of proteins, including some involved in cell proliferation. Proliferation can lead to cancer if unchecked.
This newly discovered function of p53 is surprising, says geneticist Franck Toledo of the Curie Institute's research center in Paris. He and others have studied p53's other two roles, but no one suspected the protein might also participate in the slicing and dicing of RNAs.
All three cancer-related functions require a part of the protein that latches on to specific DNA segments. Most cancers involve some disruption in p53's action, either a mutation or inactivation of the protein, Toledo says. In many tumors, the mutation lies in the portion of p53 called the DNA-binding domain.
Scientists thought that p53 could direct the production of long RNAs, called primary transcripts, which eventually are broken up into microRNAs. Previous work has shown that the p53 protein turns on production of a long RNA molecule that gets chopped into a particular microRNA.
Mutations in the protein would disrupt production of the primary transcripts, ultimately leading to lower levels of microRNAs. But the Japanese team found that primary transcripts of several microRNAs associated with cancer are made as usual in DNA-damaged cells, indicating that p53 doesn't play a role in primary transcript production. …