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Title: Autophagic Turnover of Inactive 26S Proteasomes in Yeast Is Directed by the Ubiquitin Receptor Cue5 and the Hsp42 Chaperone

The autophagic clearance of 26S proteasomes (proteaphagy) is an important homeostatic mechanism within the ubiquitin system that modulates proteolytic capacity and eliminates damaged particles. Here, we define two proteaphagy routes in yeast that respond to either nitrogen starvation or particle inactivation. Whereas the core autophagic machineries required for Atg8 lipidation and vesiculation are essential for both routes, the upstream Atg1 kinase participates only in starvation-induced proteaphagy. Following inactivation, 26S proteasomes become extensively modified with ubiquitin. Although prior studies with Arabidopsis implicated RPN10 in tethering ubiquitylated proteasomes to ATG8 lining the autophagic membranes, yeast proteaphagy employs the evolutionarily distinct receptor Cue5, which simultaneously binds ubiquitin and Atg8. Proteaphagy of inactivated proteasomes also requires the oligomeric Hsp42 chaperone, suggesting that ubiquitylated proteasomes are directed by Hsp42 to insoluble protein deposit (IPOD)-type structures before encapsulation. Together, Cue5 and Hsp42 provide a quality control checkpoint in yeast directed at recycling dysfunctional 26S proteasomes.
Authors:
 [1] ;  [2] ;  [1]
  1. Univ. of Wisconsin, Madison, WI (United States). Dept. of Genetics; Washington Univ., St. Louis, MO (United States). Dept. of Biology
  2. Washington Univ., St. Louis, MO (United States). Dept. of Biology
Publication Date:
Grant/Contract Number:
FG02-88ER13968; IOS-1339325
Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 16; Journal Issue: 6; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Research Org:
Univ. of Wisconsin, Madison, WI (United States); Washington Univ., St. Louis, MO (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Science Foundation (NSF)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; autophagy; insoluble protein deposit (IPOD); nitrogen starvation; proteaphagy; 26S proteasome; protein chaperone; ubiquitin; yeast
OSTI Identifier:
1378280
Alternate Identifier(s):
OSTI ID: 1362013