Distinct classes of misfolded proteins differentially affect the growth of yeast compromised for proteasome function. Issue 18 (17th August 2021)

• Record Type: Journal Article
• Authors: Burns, Grace D.; Hilal, Olivia E.; Sun, Zhihao; Reutter, Karl‐Richard; Preston, G. Michael; Augustine, Andrew A.; Brodsky, Jeffrey L.; Guerriero, Christopher J.
• Is Part Of: FEBS letters. Volume 595:Issue 18(2021)
• Page Start: 2383
• Page End: 2394
• Publication Date: 2021-08-17
• Subjects: chaperone -- cytoplasmic quality control -- endoplasmic reticulum associated degradation -- Hsp104 -- proteasome stress response -- protein misfolding -- quality control -- Rpn4 -- ubiquitin proteasome system -- yeast growth; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14172
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract :