PUBLICATION
Bax inhibitor 1 is a γ-secretase-independent presenilin-binding protein
- Authors
- Wu, S., Song, W., Wong, C.C.L., Shi, Y.
- ID
- ZDB-PUB-240502-20
- Date
- 2019
- Source
- Proceedings of the National Academy of Sciences of the United States of America 116: 141147141-147 (Journal)
- Registered Authors
- Keywords
- Alzheimer’s disease, Bax inhibitor 1, presenilin, β-amyloid, γ-secretase
- MeSH Terms
-
- Alzheimer Disease/metabolism
- Amyloid Precursor Protein Secretases/metabolism*
- Apoptosis Regulatory Proteins/metabolism*
- Blotting, Western
- HEK293 Cells
- Humans
- In Vitro Techniques
- Membrane Proteins/metabolism*
- Microscopy, Confocal
- Presenilin-1/metabolism
- Presenilins/metabolism*
- PubMed
- 30559186 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Wu, S., Song, W., Wong, C.C.L., Shi, Y. (2019) Bax inhibitor 1 is a γ-secretase-independent presenilin-binding protein. Proceedings of the National Academy of Sciences of the United States of America. 116:141147141-147.
Abstract
Presenilin is the catalytic subunit of γ-secretase, a four-component intramembrane protease responsible for the generation of β-amyloid (Aβ) peptides. Over 200 Alzheimer's disease-related mutations have been identified in presenilin 1 (PS1) and PS2. Here, we report that Bax-inhibitor 1 (BI1), an evolutionarily conserved transmembrane protein, stably associates with PS1. BI1 specifically interacts with PS1 in isolation, but not with PS1 in the context of an assembled γ-secretase. The PS1-BI1 complex exhibits no apparent proteolytic activity, as judged by the inability to produce Aβ40 and Aβ42 from the substrate APP-C99. At an equimolar concentration, BI1 has no impact on the proteolytic activity of γ-secretase; at a 200-fold molar excess, BI1 reduces γ-secretase activity nearly by half. Our biochemical study identified BI1 as a PS1-interacting protein, suggesting additional functions of PS1 beyond its involvement in γ-secretase.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping