Proteasome-Bound UCH37/UCHL5 Debranches Ubiquitin Chains to Promote Degradation.
Mol Cell
; 80(5): 796-809.e9, 2020 12 03.
Article
in En
| MEDLINE
| ID: mdl-33156996
ABSTRACT
The linkage, length, and architecture of ubiquitin (Ub) chains are all important variables in providing tight control over many biological paradigms. There are clear roles for branched architectures in regulating proteasome-mediated degradation, but the proteins that selectively recognize and process these atypical chains are unknown. Here, using synthetic and enzyme-derived ubiquitin chains along with intact mass spectrometry, we report that UCH37/UCHL5, a proteasome-associated deubiquitinase, cleaves K48 branched chains. The activity and selectivity toward branched chains is markedly enhanced by the proteasomal Ub receptor RPN13/ADRM1. Using reconstituted proteasome complexes, we find that chain debranching promotes degradation of substrates modified with branched chains under multi-turnover conditions. These results are further supported by proteome-wide pulse-chase experiments, which show that the loss of UCH37 activity impairs global protein turnover. Our work therefore defines UCH37 as a debranching deubiquitinase important for promoting proteasomal degradation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ubiquitin
/
Ubiquitin Thiolesterase
/
Proteasome Endopeptidase Complex
/
Intracellular Signaling Peptides and Proteins
/
Proteolysis
Limits:
Humans
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2020
Type:
Article
Affiliation country:
United States