Prion induction by the short-lived, stress-induced protein Lsb2 is regulated by ubiquitination and association with the actin cytoskeleton

Mol Cell. 2011 Jul 22;43(2):242-52. doi: 10.1016/j.molcel.2011.07.001.

Abstract

Yeast prions are self-perpetuating, QN-rich amyloids that control heritable traits and serve as a model for mammalian amyloidoses. De novo prion formation by overproduced prion protein is facilitated by other aggregated QN-rich protein(s) and is influenced by alterations of protein homeostasis. Here we explore the mechanism by which the Las17-binding protein Lsb2 (Pin3) promotes conversion of the translation termination factor Sup35 into its prion form, [PSI(+)]. We show that Lsb2 localizes with some Sup35 aggregates and that Lsb2 is a short-lived protein whose levels are controlled via the ubiquitin-proteasome system and are dramatically increased by stress. Loss of Lsb2 decreases stability of [PSI(+)] after brief heat shock. Mutations interfering with Lsb2 ubiquitination increase prion induction, while a mutation eliminating association of Lsb2 with the actin cytoskeleton blocks its aggregation and prion-inducing ability. These findings directly implicate the UPS and actin cytoskeleton in regulating prions via a stress-inducible QN-rich protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cytoskeleton / metabolism*
  • Mutation
  • Peptide Termination Factors / genetics
  • Peptide Termination Factors / metabolism
  • Prions / genetics
  • Prions / metabolism*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Stress, Physiological
  • Ubiquitination / physiology*

Substances

  • Actins
  • Carrier Proteins
  • Peptide Termination Factors
  • Prions
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • las17-binding protein Lsb2, S cerevisiae
  • Proteasome Endopeptidase Complex