Adaptability of the ubiquitin-proteasome system to proteolytic and folding stressors.
J Cell Biol
; 220(3)2021 03 01.
Article
em En
| MEDLINE
| ID: mdl-33382395
ABSTRACT
Aging, disease, and environmental stressors are associated with failures in the ubiquitin-proteasome system (UPS), yet a quantitative understanding of how stressors affect the proteome and how the UPS responds is lacking. Here we assessed UPS performance and adaptability in yeast under stressors using quantitative measurements of misfolded substrate stability and stress-dependent UPS regulation by the transcription factor Rpn4. We found that impairing degradation rates (proteolytic stress) and generating misfolded proteins (folding stress) elicited distinct effects on the proteome and on UPS adaptation. Folding stressors stabilized proteins via aggregation rather than overburdening the proteasome, as occurred under proteolytic stress. Still, the UPS productively adapted to both stressors using separate mechanisms proteolytic stressors caused Rpn4 stabilization while folding stressors increased RPN4 transcription. In some cases, adaptation completely prevented loss of UPS substrate degradation. Our work reveals the distinct effects of proteotoxic stressors and the versatility of cells in adapting the UPS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Dobramento de Proteína
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Ubiquitina
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Complexo de Endopeptidases do Proteassoma
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Proteólise
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá