From the Laboratory of Biochemistry and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892
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 (1) 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 fungus
Podospora 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. (2), focused on the evidence that
prions of yeast and fungi can serve as genetic material, and a third by
Susan Liebman and Irina Derkatch (3) 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.
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* This minireview will be reprinted in the 1999 Minireview Compendium, which will be available in December, 1999.
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