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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April 2018
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Cover Image
A 3D rendering of a Ubiquitin protein molecule. In this issue of Biochemical Society Transactions, Ovaa and Vertegaal discuss the role of ubiquitination and SUMO proteins in conjugation and deconjugation machineries; for details, see pages 423–436.
Review Article|
February 22 2018
Pseudo-DUBs as allosteric activators and molecular scaffolds of protein complexes
Miriam Walden;
Miriam Walden
1Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Astbury Building, Room 8.109, Leeds LS2 9JT, U.K.
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Safi Kani Masandi;
Safi Kani Masandi
1Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Astbury Building, Room 8.109, Leeds LS2 9JT, U.K.
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Krzysztof Pawłowski;
Krzysztof Pawłowski
2Warsaw University of Life Sciences, ul. Nowoursynowska 166, 02-787 Warszawa, Poland
3Department of Translational Medicine, Clinical Sciences, Lund University, Lund, Sweden
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Elton Zeqiraj
1Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Astbury Building, Room 8.109, Leeds LS2 9JT, U.K.
Correspondence: Elton Zeqiraj (e.zeqiraj@leeds.ac.uk)
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Publisher: Portland Press Ltd
Received:
October 16 2017
Revision Received:
January 10 2018
Accepted:
January 13 2018
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem Soc Trans (2018) 46 (2): 453–466.
Article history
Received:
October 16 2017
Revision Received:
January 10 2018
Accepted:
January 13 2018
Citation
Miriam Walden, Safi Kani Masandi, Krzysztof Pawłowski, Elton Zeqiraj; Pseudo-DUBs as allosteric activators and molecular scaffolds of protein complexes. Biochem Soc Trans 17 April 2018; 46 (2): 453–466. doi: https://doi.org/10.1042/BST20160268
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