DURHAM, N.C. -- Researchers at Duke University Medical Center have discovered that an ancient protein can perform a decidedly modern function: stimulating the immune system to fight tumors.

The protein, called calreticulin, belongs to a family of proteins called chaperones that help fold other proteins into their globular working shapes after they are synthesized as string-like molecules inside the cell. These evolutionarily ancient proteins are found in all mammalian cells and have relatives in organisms as simple as bacteria and yeast.

But calreticulin can perform another vital function, the researchers discovered. Through experiments in mice, scientists found it can act as an informant to the immune system, stimulating it to destroy skin and thymus cancers.

The two disparate functions appeared to be difficult to reconcile. But now Duke cell biologist Christopher Nicchitta has begun to resolve the mystery, demonstrating that at least two chaperone proteins appear to have evolved a dual function: assisting protein folding inside the cell and alerting the immune system if they are released from the cell, as happens when tissue is under assault from inflammation, wounding or autoimmune attack.

The discovery is described and explained in two papers in the June 1 issue of the Journal of Immunology and the July 1 issue of the Journal of Cell Science.

"Calreticulin and its relatives are complex molecules that appear to have evolved a second function," Nicchitta said. "Since they normally are found only inside the cell, when they are released they can act as a danger signal to the immune system, which responds by trying to eliminate the insult at the precise location in the body signaled by these proteins."

The work, which was supported by the National Institutes of Health, is part of Duke's Center for Genetic and Cellular Therapies continuing effort to coax the body's own immune system
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Contact: Karyn Hede
Hede0001@mc.duke.edu
919-684-4148
Duke University Medical Center
30-Jun-1999