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Updated: Oct 25, 2025

In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
Signaling Pathways Regulated by UBR Box-Containing E3 Ligases
Jung Gi Kim1,2, Ho-Chul Shin3, Taewook Seo1,2
1Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 28116, Korea.
Abstract:
UBR box E3 ligases, also called N-recognins, are integral components of the N-degron pathway. Representative N-recognins include UBR1, UBR2, UBR4, and UBR5, and they bind destabilizing N-terminal residues, termed N-degrons. Understanding the molecular bases of their substrate recognition and the biological impact of the clearance of their substrates on cellular signaling pathways can provide valuable insights into the regulation of these pathways. This review provides an overview of the current knowledge of the binding mechanism of UBR box N-recognin/N-degron interactions and their roles in signaling pathways linked to G-protein-coupled receptors, apoptosis, mitochondrial quality control, inflammation, and DNA damage. The targeting of these UBR box N-recognins can provide potential therapies to treat diseases such as cancer and neurodegenerative diseases.
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