Researchers at the University of Illinois at Chicago, working with yeast, have made the startling finding that the presence of one prion protein can spark the formation of other unrelated prions similar to the protein thought to cause “mad cow” and other diseases of mammals and man.
The researchers also devised a screening test that can be used to pinpoint unidentified prions, making it the first such genetic assay for these mysterious biological agents.
The findings are reported in the July 27 issue of the journal Cell by UIC biology professor Susan Liebman and three co-workers. A prion, the causative agent of "mad cow" disease and human Creutzfeldt-Jakob disease, is an improperly folded protein molecule that clumps together and corrupts other, healthy molecules of the same protein to do likewise, in domino fashion. When the cell divides, the corrupt protein is contained in both daughter cells, where it seeds the process again. Prions are thus infective and heritable without containing DNA or RNA as viruses do.
According to Liebman, the finding that one prion can help start the chain reaction in another, totally different protein is important, because much more is known about how prions propagate than about how they first appear—which also bears on public health concerns. Most cases of Creutzfeldt-Jakob disease, a neurodegenerative disease in humans, have no known origin, she said.
“It’s a great concern that humans can acquire CJD from infected cattle, but far, far more cases arise spontaneously,” Liebman said.
Liebman’s team devised a genetic screen for a trait in yeast that sparked the appearance of a known yeast prion. Their test identified the protein responsible for this trait and also pointed to nine other yeast prion-like proteins causing the same trait. These new prion candidates were found to contain prion-like regions in their protein chains.
“We think what we have is a general test for new prions,” Liebman said. Liebman thinks it is likely that humans have more than just the one prion, though no others are yet known, and that these prions may be related to the appearance of CJD.
“It seems unlikely that yeast would have several prions and mammals only one,” she said. “It would also seem possible that the sudden, unexplained appearance of the CJD prion may depend on other, ‘non-toxic’ prions.”
The triggering of the CJD prion by another, hidden prion may explain why CJD strikes more often in older people, Liebman said. They would have had more time to acquire silent prions. “These findings make all prions, even supposedly benign ones, more important,” she said.
Liebman’s co-authors on the Cell paper are research assistant professor Irina Derkatch, graduate student Michael Bradley and research specialist Joo Hong, all of UIC.
The research was funded by the National Institute of General Medical Sciences, one of the National Institutes of Health.
The above post is reprinted from materials provided by University Of Illinois At Chicago. Note: Materials may be edited for content and length.
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