Distinct classes of misfolded proteins differentially affect the growth of yeast compromised for proteasome function.

Autor: Burns GD; Department of Biological Sciences, University of Pittsburgh, PA, USA., Hilal OE; Department of Biological Sciences, University of Pittsburgh, PA, USA., Sun Z; Department of Biological Sciences, University of Pittsburgh, PA, USA., Reutter KR; Department of Biological Sciences, University of Pittsburgh, PA, USA., Preston GM; Department of Biological Sciences, University of Pittsburgh, PA, USA., Augustine AA; Department of Biological Sciences, University of Pittsburgh, PA, USA., Brodsky JL; Department of Biological Sciences, University of Pittsburgh, PA, USA., Guerriero CJ; Department of Biological Sciences, University of Pittsburgh, PA, USA.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2021 Sep; Vol. 595 (18), pp. 2383-2394. Date of Electronic Publication: 2021 Aug 17.
DOI: 10.1002/1873-3468.14172
Abstrakt: Maintenance of the proteome (proteostasis) is essential for cellular homeostasis and prevents cytotoxic stress responses that arise from protein misfolding. However, little is known about how different types of misfolded proteins impact homeostasis, especially when protein degradation pathways are compromised. We examined the effects of misfolded protein expression on yeast growth by characterizing a suite of substrates possessing the same aggregation-prone domain but engaging different quality control pathways. We discovered that treatment with a proteasome inhibitor was more toxic in yeast expressing misfolded membrane proteins, and this growth defect was mirrored in yeast lacking a proteasome-specific transcription factor, Rpn4p. These results highlight weaknesses in the proteostasis network's ability to handle the stress arising from an accumulation of misfolded membrane proteins.
(© 2021 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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