Emerging tools and methods to study cell signalling mediated by branched ubiquitin chains

Matthew R. McFarland; Yogesh Kulathu

doi:10.1042/BST20253015

Emerging tools and methods to study cell signalling mediated by branched ubiquitin chains

Matthew R. McFarland (Lead / Corresponding author), Yogesh Kulathu (Lead / Corresponding author)

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Abstract

Branched ubiquitin chains are complex molecular structures in which two or more ubiquitin moieties are attached to distinct lysine residues of a single ubiquitin molecule within a polyubiquitin chain. These bifurcated architectures significantly expand the signalling capacity of the ubiquitin system. Although branched chains constitute a substantial fraction of cellular polyubiquitin, their biological functions largely remain enigmatic due to their complex nature and the associated technical challenges of studying them. Recent technological innovations have enabled the identification of key molecular players and revealed essential roles for branched chains in diverse cellular processes. In this review, we discuss the bespoke strategies that have driven these
discoveries, as well as the technologies needed to advance this rapidly evolving field.

Original language	English
Number of pages	14
Journal	Biochemical Society Transactions
Early online date	16 May 2025
DOIs	https://doi.org/10.1042/BST20253015
Publication status	E-pub ahead of print - 16 May 2025

Keywords

Ubiquitin
branched ubiquitin
cell signalling
ubiquitin binding domains
chemical biology
activity based probes
deubiquitinases
proteases
protein engineering
enzymes

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10.1042/BST20253015Licence: CC BY

Final published versionFinal published version, 2.13 MBLicence: CC BY

Defining mechanisms of cellular stress responses driven by heterotypic ubiquitin chains (StressHUb)
Kulathu, Y. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/01/22 → 31/12/26
Project: Research

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title = "Emerging tools and methods to study cell signalling mediated by branched ubiquitin chains",

abstract = "Branched ubiquitin chains are complex molecular structures in which two or more ubiquitin moieties are attached to distinct lysine residues of a single ubiquitin molecule within a polyubiquitin chain. These bifurcated architectures significantly expand the signalling capacity of the ubiquitin system. Although branched chains constitute a substantial fraction of cellular polyubiquitin, their biological functions largely remain enigmatic due to their complex nature and the associated technical challenges of studying them. Recent technological innovations have enabled the identification of key molecular players and revealed essential roles for branched chains in diverse cellular processes. In this review, we discuss the bespoke strategies that have driven thesediscoveries, as well as the technologies needed to advance this rapidly evolving field.",

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AU - Kulathu, Yogesh

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N2 - Branched ubiquitin chains are complex molecular structures in which two or more ubiquitin moieties are attached to distinct lysine residues of a single ubiquitin molecule within a polyubiquitin chain. These bifurcated architectures significantly expand the signalling capacity of the ubiquitin system. Although branched chains constitute a substantial fraction of cellular polyubiquitin, their biological functions largely remain enigmatic due to their complex nature and the associated technical challenges of studying them. Recent technological innovations have enabled the identification of key molecular players and revealed essential roles for branched chains in diverse cellular processes. In this review, we discuss the bespoke strategies that have driven thesediscoveries, as well as the technologies needed to advance this rapidly evolving field.

AB - Branched ubiquitin chains are complex molecular structures in which two or more ubiquitin moieties are attached to distinct lysine residues of a single ubiquitin molecule within a polyubiquitin chain. These bifurcated architectures significantly expand the signalling capacity of the ubiquitin system. Although branched chains constitute a substantial fraction of cellular polyubiquitin, their biological functions largely remain enigmatic due to their complex nature and the associated technical challenges of studying them. Recent technological innovations have enabled the identification of key molecular players and revealed essential roles for branched chains in diverse cellular processes. In this review, we discuss the bespoke strategies that have driven thesediscoveries, as well as the technologies needed to advance this rapidly evolving field.

KW - Ubiquitin

KW - branched ubiquitin

KW - cell signalling

KW - ubiquitin binding domains

KW - chemical biology

KW - activity based probes

KW - deubiquitinases

KW - proteases

KW - protein engineering

KW - enzymes

U2 - 10.1042/BST20253015

DO - 10.1042/BST20253015

M3 - Review article

SN - 0300-5127

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

ER -

Emerging tools and methods to study cell signalling mediated by branched ubiquitin chains

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Keywords

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Defining mechanisms of cellular stress responses driven by heterotypic ubiquitin chains (StressHUb)

Cite this