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Proteasome-Bound UCH37/UCHL5 Debranches Ubiquitin Chains to Promote Degradation.
- Source :
-
Molecular cell [Mol Cell] 2020 Dec 03; Vol. 80 (5), pp. 796-809.e9. Date of Electronic Publication: 2020 Nov 05. - Publication Year :
- 2020
-
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.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- HEK293 Cells
Humans
Intracellular Signaling Peptides and Proteins genetics
Proteasome Endopeptidase Complex genetics
Ubiquitin genetics
Ubiquitin Thiolesterase genetics
Intracellular Signaling Peptides and Proteins metabolism
Proteasome Endopeptidase Complex metabolism
Proteolysis
Ubiquitin metabolism
Ubiquitin Thiolesterase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 80
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 33156996
- Full Text :
- https://doi.org/10.1016/j.molcel.2020.10.017