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Updated: May 3, 2026

Reporter-based Growth Assay for Systematic Analysis of Protein Degradation
Published on: November 6, 2014
Sorting out the trash: the spatial nature of eukaryotic protein quality control
Emily Mitchell Sontag1, Willianne I M Vonk1, Judith Frydman1
1Department of Biology, Stanford University, Stanford, California 94305, USA.
Abstract:
Failure to maintain protein homeostasis is associated with aggregation and cell death, and underies a growing list of pathologies including neurodegenerative diseases, aging, and cancer. Misfolded proteins can be toxic and interfere with normal cellular functions, particularly during proteotoxic stress. Accordingly, molecular chaperones, the ubiquitin-proteasome system (UPS) and autophagy together promote refolding or clearance of misfolded proteins. Here we discuss emerging evidence that the pathways of protein quality control (PQC) are intimately linked to cell architecture, and sequester proteins into spatially and functionally distinct PQC compartments. This sequestration serves a number of functions, including enhancing the efficiency of quality control; clearing the cellular milieu of potentially toxic species and facilitating asymmetric inheritance of damaged proteins to promote rejuvenation of daughter cells.
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