Pseudo-DUBs as allosteric activators and molecular scaffolds of protein complexes

Biochemical Society Transactions
Miriam WaldenElton Zeqiraj

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 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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Citations

Sep 24, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sarah Zachariah, Douglas A Gray
Dec 18, 2019·Biochemical Society Transactions·Almut Dufner, Klaus-Peter Knobeloch
May 31, 2019·Nature·Miriam WaldenElton Zeqiraj
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Feb 9, 2019·Nature Reviews. Molecular Cell Biology·Michael J ClagueDavid Komander
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Dec 19, 2020·Cell Death and Differentiation·Mohammed A BasarAchim Werner
Nov 19, 2021·Inflammopharmacology·Niraj Parihar, Lokesh Kumar Bhatt

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