Pseudo-DUBs as allosteric activators and molecular scaffolds of protein complexes
(2018) In Biochemical Society Transactions 46(2). p.453-466- Abstract
The ubiquitin (Ub) proteasome system and Ub signalling networks are crucial to cell biology and disease development. Deubiquitylases (DUBs) control cell signalling by removing mono-Ub and polyubiquitin chains from substrates. DUBs take part in almost all processes that regulate cellular life and are frequently dysregulated in disease. We have catalogued 99 currently known DUBs in the human genome and sequence conservation analyses of catalytic residues suggest that 11 lack enzyme activity and are classed as pseudo-DUBs. These pseudoenzymes play important biological roles by allosterically activating catalytically competent DUBs as well as other active enzymes. Additionally, pseudoenzymes act as assembly scaffolds of macromolecular... (More)
The ubiquitin (Ub) proteasome system and Ub signalling networks are crucial to cell biology and disease development. Deubiquitylases (DUBs) control cell signalling by removing mono-Ub and polyubiquitin chains from substrates. DUBs take part in almost all processes that regulate cellular life and are frequently dysregulated in disease. We have catalogued 99 currently known DUBs in the human genome and sequence conservation analyses of catalytic residues suggest that 11 lack enzyme activity and are classed as pseudo-DUBs. These pseudoenzymes play important biological roles by allosterically activating catalytically competent DUBs as well as other active enzymes. Additionally, pseudoenzymes act as assembly scaffolds of macromolecular complexes. We discuss how pseudo-DUBs have lost their catalytic activity, their diverse mechanisms of action and their potential as therapeutic targets. Many known pseudo-DUBs play crucial roles in cell biology and it is likely that unstudied and overlooked pseudo-DUB genes will have equally important functions.
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- author
- Walden, Miriam ; Masandi, Safi Kani ; Pawłowski, Krzysztof LU and Zeqiraj, Elton
- organization
- publishing date
- 2018-04-17
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochemical Society Transactions
- volume
- 46
- issue
- 2
- pages
- 14 pages
- publisher
- Biochemical Society
- external identifiers
-
- scopus:85046885999
- pmid:29472364
- ISSN
- 0300-5127
- DOI
- 10.1042/BST20160268
- language
- English
- LU publication?
- yes
- id
- 9f7598fb-2f9d-4d06-8de8-ec129a943b4f
- date added to LUP
- 2018-05-24 14:51:48
- date last changed
- 2024-04-15 07:17:19
@article{9f7598fb-2f9d-4d06-8de8-ec129a943b4f,
abstract = {{<p>The ubiquitin (Ub) proteasome system and Ub signalling networks are crucial to cell biology and disease development. Deubiquitylases (DUBs) control cell signalling by removing mono-Ub and polyubiquitin chains from substrates. DUBs take part in almost all processes that regulate cellular life and are frequently dysregulated in disease. We have catalogued 99 currently known DUBs in the human genome and sequence conservation analyses of catalytic residues suggest that 11 lack enzyme activity and are classed as pseudo-DUBs. These pseudoenzymes play important biological roles by allosterically activating catalytically competent DUBs as well as other active enzymes. Additionally, pseudoenzymes act as assembly scaffolds of macromolecular complexes. We discuss how pseudo-DUBs have lost their catalytic activity, their diverse mechanisms of action and their potential as therapeutic targets. Many known pseudo-DUBs play crucial roles in cell biology and it is likely that unstudied and overlooked pseudo-DUB genes will have equally important functions.</p>}},
author = {{Walden, Miriam and Masandi, Safi Kani and Pawłowski, Krzysztof and Zeqiraj, Elton}},
issn = {{0300-5127}},
language = {{eng}},
month = {{04}},
number = {{2}},
pages = {{453--466}},
publisher = {{Biochemical Society}},
series = {{Biochemical Society Transactions}},
title = {{Pseudo-DUBs as allosteric activators and molecular scaffolds of protein complexes}},
url = {{http://dx.doi.org/10.1042/BST20160268}},
doi = {{10.1042/BST20160268}},
volume = {{46}},
year = {{2018}},
}