Evolution Has Led to More Efficient Tumor Suppression

Researchers have found that the Arf gene, known to activate the tumor-suppressing p53 gene, also displays a cancer-suppressing effect of its own by inhibiting production of ribosomal RNA. Their findings were reported in the February 2003 issue of Molecular Cell.

Previous studies had shown that Arf was involved in cancer suppression through its activation of the tumor-suppressing gene, p53. In the current study, investigators from St. Jude Children's Research Hospital (Memphis, TN, USA) extended the inquiry into the role of Arf by infecting a variety of mouse cells with viral vectors containing the Arf gene. Results showed that Arf interfered with production of the RNA components of ribosomes. Modulation of ribosomal RNA production allowed the gene to exert some control of protein production and cell growth.

"About 80% of a cell's RNA is tied up in ribosomes,” explained senior author Dr. Charles Sherr, an investigator in the genetics & tumor cell biology department at St. Jude Children's Research Hospital. "In fact, producing ribosomes is practically what cells do for a living. It is their major energy-consuming activity. So it makes sense that any limitation on ribosome production would slow cell growth.”

The researchers believe that the regulation of ribosomal RNA production is an older control mechanism than activation of p53. Inhibition of ribosomal production is not a particularly efficient way to control cell growth, while p53 activates many growth-suppressive genes. Therefore Dr. Sherr feels that, "Arf appears to have become more efficient because, by evolving a way to activate p53, it was able to extend its reach and inhibit many more cellular responses apart from ribosome synthesis.”



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