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A ubiquitin‐binding CUE domain in presenilin‐1 enables interaction with K63‐linked polyubiquitin chains
Author(s) -
Duggan Stephen P.,
Yan Run,
McCarthy Justin V.
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.03.008
Subject(s) - presenilin , ubiquitin , endoplasmic reticulum , proteolysis , microbiology and biotechnology , transmembrane protein , biochemistry , function (biology) , transmembrane domain , amyloid precursor protein secretase , amyloid precursor protein , chemistry , biology , enzyme , amino acid , receptor , alzheimer's disease , medicine , disease , pathology , gene
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.