Prion induction by the short-lived, stress-induced protein Lsb2 is regulated by ubiquitination and association with the actin cytoskeleton.
Mol Cell
; 43(2): 242-52, 2011 Jul 22.
Article
em En
| MEDLINE
| ID: mdl-21777813
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto
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Príons
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Proteínas de Transporte
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Actinas
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Proteínas de Saccharomyces cerevisiae
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Ubiquitinação
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article