Abstract:
:Cellular toxicity introduced by protein misfolding threatens cell fitness and viability. Failure to eliminate these polypeptides is associated with various aggregation diseases. In eukaryotes, the ubiquitin proteasome system (UPS) plays a vital role in protein quality control (PQC), by selectively targeting misfolded proteins for degradation. While the assembly of the proteasome can be naturally impaired by many factors, the regulatory pathways that mediate the sorting and elimination of misassembled proteasomal subunits are poorly understood. Here, we reveal how the dysfunctional proteasome is controlled by the PQC machinery. We found that among the multilayered quality control mechanisms, UPS mediated degradation of its own misassembled subunits is the favored pathway. We also demonstrated that the Hsp42 chaperone mediates an alternative pathway, the accumulation of these subunits in cytoprotective compartments. Thus, we show that proteasome homeostasis is controlled through probing the level of proteasome assembly, and the interplay between UPS mediated degradation or their sorting into distinct cellular compartments.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Peters LZ,Karmon O,David-Kadoch G,Hazan R,Yu T,Glickman MH,Ben-Aroya Sdoi
10.1371/journal.pgen.1005178subject
Has Abstractpub_date
2015-04-28 00:00:00pages
e1005178issue
4eissn
1553-7390issn
1553-7404pii
PGENETICS-D-14-01622journal_volume
11pub_type
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