title: Prion induction by the short-lived, stress-induced protein Lsb2 is regulated by ubiquitination and association with the actin cytoskeleton.
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.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Chernova
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Romanyuk
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Karpova
authors.forename: John R
authors.initials: JR
authors.lastname: Shanks
authors.forename: Moiez
authors.initials: M
authors.lastname: Ali
authors.forename: Nela
authors.initials: N
authors.lastname: Moffatt
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Howie
authors.forename: Andrew
authors.initials: A
authors.lastname: O'Dell
authors.forename: James G
authors.initials: JG
authors.lastname: McNally
authors.forename: Susan W
authors.initials: SW
authors.lastname: Liebman
authors.forename: Yury O
authors.initials: YO
authors.lastname: Chernoff
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wilkinson
mesh_terms: D000199:Actins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D009154:Mutation; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D000199:Actins; D002352:Carrier Proteins; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C568808:las17-binding protein Lsb2, S cerevisiae; D046988:Proteasome Endopeptidase Complex