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

TY - JOUR

T1 - Emerging tools and methods to study cell signalling mediated by branched ubiquitin chains

AU - McFarland, Matthew R.

AU - Kulathu, Yogesh

N1 - Publisher Copyright: © 2025 The Author(s).

PY - 2025/6/30

Y1 - 2025/6/30

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 these discoveries, 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 these discoveries, 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

KW - activity-based probes

UR - https://www.scopus.com/pages/publications/105009850946

U2 - 10.1042/BST20253015

DO - 10.1042/BST20253015

M3 - Review article

SN - 0300-5127

VL - 53

SP - 579

EP - 592

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

IS - 3

ER -