A ubiquitin‐binding CUE domain in presenilin‐1 enables interaction with K63‐linked polyubiquitin chains
Open accessAbstract
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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Presenilin proteins can be ubiquitinated.
“In previous studies it has been shown that presenilin proteins can be ubiquitinated.51, 52”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [52]
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Research works printed but not linked: 2
- [19][19] [Shih, S.C., Prag, G., Francis, S.A., Sutanto, M.A., Hurley, J.H. and Hicke, L. (2003) A ubiquitin-binding motif required for intramolecular monoubiquitylation, the CUE domain. EMBO J. 22, 1273-1281.](http://refhub.elsevier.com/S0014-5793(15)00156-8/h0095) -
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Sorted by citations
APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease
Vélez, J. I., Lopera, F., Sepulveda-Falla, D., Patel, H. R., Johar, A. S., Chuah, A., Tobón, C., Rivera, D., Villegas, A., Cai, Y., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.177 · Cited by 111 · see citing works
- Authors
- Duggan, S. P., Yan, R., & McCarthy, J. V.
- Affiliations
- University College Cork (IE)
- Corresponding author
- McCarthy, Justin V.
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2015-03-18
- Volume
- 589
- Issue
- 9
- Pages
- 1001-1008
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2114689657
- Cited by
- 10
- References
- 48
- Citations by year
- 2025: 1 · 2024: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2015: 3
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Irish Research Council for Science, Engineering and Technology (RS/2009/1245, RS/2012/407)
- Science Foundation Ireland (09/IN.1/B2624)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- presenilin 1, CUE domain, ubiquitin-binding domain, gamma-secretase, regulated intramembrane proteolysis, presenilin 2, amyloid precursor protein, notches, protein-protein interaction
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Cells, Cultured, Humans, Lysine, Molecular Sequence Data, Mutation, Peptide Fragments, Protein Binding, Blotting, Western, Signal Transduction, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Sequence Homology, Amino Acid, Ubiquitin, Polyubiquitin, Mice, Presenilin-1, Amyloid Precursor Protein Secretases, HEK293 Cells, Proteolysis
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