sealPurdue News
____

November 8, 1990

Protein That Could Aid In Cancer Is Linked To Black Plague

West Lafayette, Ind. – Researchers at Purdue University's Department of Biochemistry have discovered a link between a protein that helps regulate the growth of cells, and the bacteria that caused the bubonic plague and killed a fourth of the population of Europe during the Middle Ages.

Their discovery provides scientists with their first example of a bacterium containing a protein of this type. Their studies may help scientists understand how cells regulate their own growth and may someday help in understanding and treating cancer.

Professor Jack E. Dixon and Kunliang Guan, a postdoctoral fellow at Purdue, were studying a protein called tyrosine phosphatase (FAHS-fo-tase), which they believe may reverse some effects of other proteins that can cause cancer.

During the course of their studies, they found that protein tyrosine phosphatase also was present in the bacteria that caused outbreaks of bubonic plague in 1348 and 1665.

The findings were reported in the Aug. 3 issue of Science, the journal of the American Association for the Advancement of Science. Dixon will present a talk on their discovery Monday (11/12) at the Walther Cancer Institute in Indianapolis.

"We have known that certain kinds of proteins will take a normal cell and transform it into an abnormal cell, which may lead to unrestrained cell growth -- one of the major traits of cancer," Dixon says. "We have evidence that the protein tyrosine phosphatase, however, can reverse some of these effects."

It does so by reacting with another enzyme to remove phosphorus from the cell. This process in turn helps regulate the rate at which cells grow and proliferate, Dixon says.

He compares the process to the operation of a light switch. Normally in a cell, the lights would be turned off, and cells would grow and divide at a regulated pace. Certain proteins can switch the lights on, causing unrestrained cell growth. But presence of protein tyrosine phosphatase can turn the lights off in the cell and allow the cell to function normally again.

While searching a database to find similar proteins, Dixon and Guan discovered that a protein found in bacteria known as Yersinia -- the bacterium responsible for bubonic plague -- had the same "molecular fingerprint" as protein tyrosine phosphatase.

"We now know that the protein we looked at in Yersinia was a tyrosine phosphatase protein," he says.

Dixon and Guan obtained a sample of the protein in Yersinia and found that it operates in a cell the same way as protein tyrosine phosphatase does -- it slows and, ultimately, can stop cell growth.

Dixon says this is probably why the bacteria that caused the plague had such devastating effects in people. (Dixon says once the phosphatase gene is isolated from its normal environment, the Yersinia bacterium, it is no longer a health threat to produce the gene and look at its activity.)

Their discovery has led scientists to question how the protein tyrosine phosphatase entered the bacterium, and how it worked within the cell to disable cell growth.

"It may also suggest that bacteria and viruses in other diseases could use the same pathways to enter cells and exert their negative effects," says Guan.

Dixon says the discovery isn't likely to lead to a cure for the plague, which still claims lives. A few cases are reported each year in the western United States, and outbreaks occur in Third World countries, where sanitation is a problem. It can, however, be controlled by antibiotics if diagnosed in time.

But their findings could help find ways to treat cancer by improving the understanding of the uncontrolled cell growth that characterizes the disease.

"It may have important implications as far as cancer is concerned," he says.

Research in the Purdue biochemistry laboratory is continuing on related topics. Jim Clemens, a graduate student, is looking for similar genes in other disease-causing bacteria. Terry Woodford, a postdoctoral fellow, is studying how phosphatases can slow cell growth.

Funding for the research came from the National Institutes of Health and the Walther Cancer Institute.

Purdue News Service: (765) 494-2096; purduenews@purdue.edu


* To the Purdue News and Photos Page