Journal article
Deubiquitinases in muscle physiology and disorders
- Abstract:
- In vivo, muscle and neuronal cells are post-mitotic, and their function is predominantly regulated by proteostasis, a multilayer molecular process that maintains a delicate balance of protein homeostasis. The ubiquitin-proteasome system (UPS) is a key regulator of proteostasis. A dysfunctional UPS is a hallmark of muscle ageing and is often impacted in neuromuscular disorders (NMDs). Malfunction of the UPS often results in aberrant protein accumulation which can lead to protein aggregation and/or mis-localization affecting its function. Deubiquitinating enzymes (DUBs) are key players in the UPS, controlling protein turnover and maintaining the free ubiquitin pool. Several mutations in DUB encoding genes are linked to human NMDs, such as ATXN3, OTUD7A, UCHL1 and USP14, whilst other NMDs are associated with dysregulation of DUB expression. USP5, USP9X and USP14 are implicated in synaptic transmission and remodeling at the neuromuscular junction. Mice lacking USP19 show increased maintenance of lean muscle mass. In this review, we highlight the involvement of DUBs in muscle physiology and NMDs, particularly in processes affecting muscle regeneration, degeneration and inflammation following muscle injury. DUBs have recently garnered much respect as promising drug targets, and their roles in muscle maturation, regeneration and degeneration may provide the framework for novel therapeutics to treat muscular disorders including NMDs, sarcopenia and cachexia.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 990.6KB, Terms of use)
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- Publisher copy:
- 10.1042/bst20230562
Authors
- Publisher:
- Portland Press
- Journal:
- Biochemical Society transactions More from this journal
- Volume:
- 52
- Issue:
- 3
- Article number:
- BST20230562
- Place of publication:
- England
- Publication date:
- 2024-05-08
- Acceptance date:
- 2024-04-23
- DOI:
- EISSN:
-
1470-8752
- ISSN:
-
0300-5127
- Pmid:
-
38716888
- Language:
-
English
- Keywords:
- Pubs id:
-
1995383
- Local pid:
-
pubs:1995383
- Deposit date:
-
2024-07-05
Terms of use
- Copyright holder:
- Ollie et al.
- Copyright date:
- 2024
- Rights statement:
- © 2024 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). Open access for this article was enabled by the participation of University of Oxford in an all-inclusive Read & Publish agreement with Portland Press and the Biochemical Society under a transformative agreement with JISC.
- Licence:
- CC Attribution (CC BY)
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