title: A ubiquitin-binding CUE domain in presenilin-1 enables interaction with K63-linked polyubiquitin chains.
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.
authors: Signal Transduction Laboratory, School of Biochemistry and Cell Biology, ABCRF, Western Gateway Building, Western Road, University College Cork, Cork, Ireland.
authors: Stephen P
authors: SP
authors: Duggan
authors: Signal Transduction Laboratory, School of Biochemistry and Cell Biology, ABCRF, Western Gateway Building, Western Road, University College Cork, Cork, Ireland.
authors: Run
authors: R
authors: Yan
authors: Signal Transduction Laboratory, School of Biochemistry and Cell Biology, ABCRF, Western Gateway Building, Western Road, University College Cork, Cork, Ireland. Electronic address: jv.mccarthy@ucc.ie.
authors: Justin V
authors: JV
authors: McCarthy
mesh_terms: D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D025821:Polyubiquitin / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D053764:Presenilin-1; D025801:Ubiquitin; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D025821:Polyubiquitin; D053829:Amyloid Precursor Protein Secretases; D008239:Lysine
keywords: CUE domain; Presenilin; Signaling; Ubiquitin; γ-Secretase