Signaling Pathways Regulated by UBR Box-Containing E3 Ligases

• Main Authors: Jung Gi Kim, Ho-Chul Shin, Taewook Seo, Laxman Nawale, Goeun Han, Bo Yeon Kim, Seung Jun Kim, Hyunjoo Cha-Molstad
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: UBR Box E3 ligases; N-recognin; Arg/N-degron pathway; N-degron; G-protein signaling; apoptosis
• Online Access: https://www.mdpi.com/1422-0067/22/15/8323

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.