title: Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the yeast [PSI(+)] prion.
abstract: The yeast prion [PSI(+)] results from self-propagating aggregates of Sup35p. De novo formation of [PSI(+)] requires an additional non-Mendelian trait, thought to result from a prion form of one or more unknown proteins. We find that the Gln/Asn-rich prion domains of two proteins, New1p and Rnq1p, can control susceptibility to [PSI(+)] induction as well as enhance aggregation of a human glutamine expansion disease protein. [PSI(+)] inducibility results from gain-of-function properties of New1p and Rnq1p aggregates rather than from inactivation of the normal proteins. These studies suggest a molecular basis for the epigenetic control of [PSI(+)] inducibility and may reveal a broader role for this phenomenon in the physiology of protein aggregation.
authors.affiliation: Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. lxoshe@itsa.ucsf.edu
authors.forename: L Z
authors.initials: LZ
authors.lastname: Osherovich
authors.forename: J S
authors.initials: JS
authors.lastname: Weissman
mesh_terms: D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000067699:Ataxin-3; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005800:Genes, Fungal / Q000235:genetics; D005973:Glutamine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017827:Machado-Joseph Disease / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins; D010454:Peptide Termination Factors; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D005656:Fungal Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010454:Peptide Termination Factors; D010455:Peptides; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005973:Glutamine; C097188:polyglutamine; D001216:Asparagine; C092341:ATXN3 protein, human; D000067699:Ataxin-3