title: Molecular chaperone Hsp104 can promote yeast prion generation.
abstract: [URE3] is an amyloid-based prion of Ure2p, a regulator of nitrogen catabolism in Saccharomyces cerevisiae. The Ure2p of the human pathogen Candida albicans can also be a prion in S. cerevisiae. We find that overproduction of the disaggregating chaperone, Hsp104, increases the frequency of de novo [URE3] prion formation by the Ure2p of S. cerevisiae and that of C. albicans. This stimulation is strongly dependent on the presence of the [PIN(+)] prion, known from previous work to enhance [URE3] prion generation. Our data suggest that transient Hsp104 overproduction enhances prion generation through persistent effects on Rnq1 amyloid, as well as during overproduction by disassembly of amorphous Ure2 aggregates (generated during Ure2p overproduction), driving the aggregation toward the amyloid pathway. Overproduction of other major cytosolic chaperones of the Hsp70 and Hsp40 families (Ssa1p, Sse1p, and Ydj1p) inhibit prion formation, whereas another yeast Hsp40, Sis1p, modulates the effects of Hsp104p on both prion induction and prion curing in a prion-specific manner. The same factor may both enhance de novo prion generation and destabilize existing prion variants, suggesting that prion variants may be selected by changes in the chaperone network.
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0830, USA.
authors.forename: Dmitry S
authors.initials: DS
authors.lastname: Kryndushkin
authors.forename: Abbi
authors.initials: A
authors.lastname: Engel
authors.forename: Herman
authors.initials: H
authors.lastname: Edskes
authors.forename: Reed B
authors.initials: RB
authors.lastname: Wickner
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014170:Transformation, Genetic
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010454:Peptide Termination Factors; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; C070320:SIS1 protein, S cerevisiae; C494656:SSE1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070319:YDJ1 protein, S cerevisiae; C070972:HsP104 protein, S cerevisiae; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae