Recurrent background mutations in WHI2 impair proteostasis and degradation of misfolded cytosolic proteins in Saccharomyces cerevisiae
Abstract Proteostasis promotes viability at both the cellular and organism levels by maintaining a functional proteome. This requires an intricate protein quality control (PQC) network that mediates protein folding by molecular chaperones and removes terminally misfolded proteins via the ubiquitin p...
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| Autores principales: | , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/64f77dfa53a840999b4b6e1865581fdb |
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| Sumario: | Abstract Proteostasis promotes viability at both the cellular and organism levels by maintaining a functional proteome. This requires an intricate protein quality control (PQC) network that mediates protein folding by molecular chaperones and removes terminally misfolded proteins via the ubiquitin proteasome system and autophagy. How changes within the PQC network can perturb proteostasis and shift the balance between protein folding and proteolysis remain poorly understood. However, given that proteostasis is altered in a number of conditions such as cancer and ageing, it is critical that we identify the factors that mediate PQC and understand the interplay between members of the proteostatic network. In this study, we investigated the degradation of a thermally unstable cytosolic model substrate and identified a surprisingly high number of strains in the yeast knockout collection that displayed impaired turnover of the misfolded substrate. We found that this phenotype was caused by frequent background mutations in the general stress response gene WHI2. We linked this proteostatic defect to the lack of activity of the stress response transcription factor Msn2, potentially under conditions where the TOR pathway is active. Our results underscore how changes to the elaborate PQC network can perturb proteostasis and impair degradation of misfolded cytosolic proteins. |
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