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Updated: Apr 16, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
A ubiquitin-binding CUE domain in presenilin-1 enables interaction with K63-linked polyubiquitin chains
Stephen P Duggan1, Run Yan1, Justin V McCarthy1
1Signal Transduction Laboratory, School of Biochemistry and Cell Biology, ABCRF, Western Gateway Building, Western Road, University College Cork, Cork, Ireland.
Abstract:
The presenilins (PS1 and PS2) are the catalytic component of the γ-secretase intramembrane protease complex, involved in the regulated intramembrane proteolysis of numerous type I transmembrane proteins, including amyloid precursor protein (APP) and Notch. Herein, we describe the identification and characterization of a CUE (coupling of ubiquitin conjugation to endoplasmic reticulum degradation) ubiquitin-binding domain (UBD) in PS1, and demonstrate that the CUE domain of PS1 mediates non-covalent binding to Lysine 63-linked polyubiquitin chains. Our results highlight a γ-secretase-independent function for non-covalent ubiquitin signaling in the regulation of PS1, and add new insights into the structure and function of the presenilin proteins.
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