The Protein Quality Control Machinery Regulates Its Misassembled Proteasome Subunits

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The accumulation of misfolded proteins threatens cell fitness and viability and their aggregation is commonly associated with numerous neurodegenerative disorders. Cells therefore rely on a number of protein quality control (PQC) pathways to prevent protein aggregation. In eukaryotes, the ubiquitin proteasome system (UPS), a supramolecular machinery that mediates the proteolysis of damaged or misfolded proteins, plays a vital role in PQC by selectively targeting proteins for degradation. Although the critical role-played by the UPS in PQC, and the severe consequences of impairing this pathway are well established, little was known about the mechanisms that control dysfunctional proteasome subunits. Here, we reveal that the interplay between UPS mediated degradation of its own misassembled subunits, and sorting them into cytoprotective compartments, a process that is mediated by the Hsp42 chaperone, determines how proteasome homeostasis is controlled in yeast cells. We believe that the mechanism of proteasome regulation by the PCQ in yeast may serve as a paradigm for understanding how homeostasis of this essential complex is controlled in major chronic neurodegenerative disorders in higher eukaryotes.

Vyšlo v časopise: The Protein Quality Control Machinery Regulates Its Misassembled Proteasome Subunits. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005178
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005178

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