Prions of Mammals and Fungi Minireview Series

The mammalian spongiform encephalopathies gave rise to the concept of infectious proteins, proteins that can transmit an infection without an essential nucleic acid. This concept is now identified with the term “prion.” These diseases, including scrapie of sheep, bovine spongiform encephalopathy, and human Creutzfeldt-Jakob disease (and its variants), are believed to be the result of a self-propagating change of PrP, a cell surface protein. The minireview in this issue by Charles Weissmann (1Weissmann C. J. Biol. Chem. 1999; 274: 3-6Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar) examines the spongiform encephalopathies and summarizes work from a number of laboratories. In 1994, it was suggested that two non-chromosomal genetic elements of Saccharomyces cerevisiae, [URE3] and [PSI], were infectious protein (prion) forms of Ure2p and Sup35p. These findings have been particularly exciting because these systems will permit the application of the powerful genetic methods available in yeast to the study of the prion problem. Recently, [Het-s], a non-Mendelian genetic element of the filamentous fungusPodospora anserina has been identified as another likely prion. In each case, the evidence points to an altered form of a chromosomally encoded protein that has acquired the ability to convert the normal form of the protein into the same altered (prion) abnormal form. These new developments will be summarized in a second minireview by Reed Wickner et al. (2Wickner R.B. Edskes H.K. Maddelein M.-L. Taylor K. Moriyama H. J. Biol. Chem. 1999; 274: 555-558Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar), focused on the evidence that prions of yeast and fungi can serve as genetic material, and a third by Susan Liebman and Irina Derkatch (3Leibman S.W. Derkatch I.L. J. Biol. Chem. 1999; 274: 1181-1184Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar) discussing the yeast [PSI+] prion in detail, including its interactions with chaperones and other proteins. Although the epidemic of “mad cow disease” has brought this field to the headlines, its scientific excitement rests more on the notion that altered protein conformations can impart disease and the somewhat revolutionary concepts of infection and heredity that have come out of this work.