The protein quality control machinery regulates its misassembled proteasome subunits.
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.
Faculty of Life Sciences Bar-Ilan University, Ramat-Gan, Israel.
Lee Zeev
LZ
Peters
Faculty of Life Sciences Bar-Ilan University, Ramat-Gan, Israel.
Ofri
O
Karmon
Faculty of Life Sciences Bar-Ilan University, Ramat-Gan, Israel.
Galit
G
David-Kadoch
Faculty of Life Sciences Bar-Ilan University, Ramat-Gan, Israel.
Rotem
R
Hazan
Departement of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Tzenlin
T
Yu
Departement of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Michael H
MH
Glickman
Faculty of Life Sciences Bar-Ilan University, Ramat-Gan, Israel.
Shay
S
Ben-Aroya
D002470:Cell Survival / Q000235:genetics*; D056084:Genetic Fitness; D006360:Heat-Shock Proteins / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D017510:Protein Folding; D059748:Proteolysis; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics
C098005:HSP42 protein, S cerevisiae; D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex