Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the yeast [PSI(+)] prion

Cell. 2001 Jul 27;106(2):183-94. doi: 10.1016/s0092-8674(01)00440-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Asparagine / chemistry
  • Asparagine / genetics
  • Asparagine / metabolism*
  • Ataxin-3
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression
  • Genes, Fungal / genetics
  • Glutamine / chemistry
  • Glutamine / genetics
  • Glutamine / metabolism*
  • Humans
  • Machado-Joseph Disease / metabolism
  • Microscopy, Fluorescence
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins
  • Peptide Termination Factors
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism
  • Phenotype
  • Prions / chemistry*
  • Prions / genetics
  • Prions / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*

Substances

  • Fungal Proteins
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Peptide Termination Factors
  • Peptides
  • Prions
  • RNQ1 protein, S cerevisiae
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Glutamine
  • polyglutamine
  • Asparagine
  • ATXN3 protein, human
  • Ataxin-3