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Evolution boosted anti-cancer prowess of a primordial gene

Researchers at St. Jude Children's Research Hospital have looked back in evolutionary time and identified what may be a gene that was once only moderately effective in slowing down cellular reproduction, until it linked up with a more efficient set of genes to create a powerful anti-cancer response.

The gene, called Arf, was already known to have cancer-suppressing activity. Arf responds to cancer-causing environments by activating the well-known tumor suppressor gene, p53. In turn, p53 activates a battery of other genes to stop cell growth or, in extreme cases, to trigger cell death in response to a variety of harmful conditions, such as DNA damage or activation of oncogenes (cancer-causing genes). In fact, loss of Arf or p53 is a common event in many human cancers.

But the new results suggest that Arf plays a role far older in evolutionary terms than its more familiar job of stimulating p53 to prevent cancer. The St. Jude findings suggest that Arf originally evolved to slow the cell's metabolism and growth by limiting production of ribosomes. Ribosomes, made up of RNA (de-coded DNA) and proteins, guide the production of all other cellular proteins according to the genetic code. The new work shows that Arf interferes with production of the RNA components of ribosomes in order to exert some control of protein production and cell growth.

"About 80 percent of a cell's RNA is tied up in ribosomes," said Charles Sherr, M.D., Ph.D., a member of the Genetics & Tumor Cell Biology Department at St. Jude and a Howard Hughes Medical Institute investigator. "In fact, producing ribosomes is practically what cells do for a living. It's their major energy-consuming activity. So it makes sense that any limitation on ribosome production would slow cell growth."

Sherr's team believes that Arf counteracts excessive growth-promoting stimuli by interfering with ribosome production. But inhibiting ribosomal production isn't a particularly efficient way to control
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
3-Mar-2003


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