A ubiquitin-binding CUE domain in presenilin-1 enables interaction with K63-linked polyubiquitin chains

作者：Duggan Stephen P; Yan Run; McCarthy Justin V^*

来源：FEBS LETTERS, 2015, 589(9): 1001-1008.

DOI：10.1016/j.febslet.2015.03.008

• Presenilin
• gamma-Secretase
• Ubiquitin
• CUE domain
• Signaling

The presenilins (PS1 and PS2) are the catalytic component of the gamma-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 gamma-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.

• 出版日期2015-4-13