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

FEBS Letters

article

Grace D. Burns¹  Olivia E. Hilal¹  Zhihao Sun¹  Karl-Richard Reutter¹  G. Michael Preston¹  Andrew A. Augustine¹  Jeffrey L. Brodsky¹  Christopher J. Guerriero¹ 

[1] Department of Biological Sciences, University of Pittsburgh

关键词: chaperone;    cytoplasmic quality control;    endoplasmic reticulum associated degradation;    Hsp104;    proteasome stress response;    protein misfolding;    quality control;    Rpn4;    ubiquitin proteasome system;    yeast growth;   

DOI  :  10.1002/1873-3468.14172

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown