ArticleBiophysical journal2015
Intramembrane proteolysis of β-amyloid precursor protein by γ-secretase is an unusually slow process.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 69 citations in OpenAlex.
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Conformational Flexibility of Transmembrane Helices: How it Works and Where it Matters.Chemical reviews · 2026Review
- A C. elegans model of familial Alzheimer's disease shows age-dependent synaptic degeneration independent of amyloid β-peptide.Neurobiology of disease · 2026Article
- Enzyme-substrate hybrid β-sheet controls geometry and water access to the γ-secretase active site.Communications biology · 2023Article
- Cooperation of N- and C-terminal substrate transmembrane domain segments in intramembrane proteolysis by γ-secretase.Communications biology · 2023Article
- Rhomboid-catalyzed intramembrane proteolysis requires hydrophobic matching with the surrounding lipid bilayer.Science advances · 2022Article
- Structure and mechanism of the γ-secretase intramembrane protease complex.Current opinion in structural biology · 2022Review
- Mechanism of Tripeptide Trimming of Amyloid β-Peptide 49 by γ-Secretase.Journal of the American Chemical Society · 2022Article
- Effect of Environmental Factors on the Catalytic Activity of Intramembrane Serine Protease.Journal of the American Chemical Society · 2022Article
- Challenges and frontiers of computational modelling of biomolecular recognition.QRB discovery · 2022Article
- Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?Cancer metastasis reviews · 2020Review
- Physiological functions of SPP/SPPL intramembrane proteases.Cellular and molecular life sciences : CMLS · 2020Review
- Mechanisms of γ-Secretase Activation and Substrate Processing.ACS central science · 2020Article
- Signaling Functions of Intramembrane Aspartyl-Proteases.Frontiers in cardiovascular medicine · 2020Review
- Modulating Hinge Flexibility in the APP Transmembrane Domain Alters γ-Secretase Cleavage.Biophysical journal · 2019Article
- Influence of the familial Alzheimer's disease-associated T43I mutation on the transmembrane structure and γ-secretase processing of the C99 peptide.The Journal of biological chemistry · 2019Article
- Membrane-associated epithelial cell adhesion molecule is slowly cleaved by γ-secretase prior to efficient proteasomal degradation of its intracellular domain.The Journal of biological chemistry · 2019Article
- Rhomboid distorts lipids to break the viscosity-imposed speed limit of membrane diffusion.Science (New York, N.Y.) · 2019Article
- Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intramembrane proteolysis has emerged as a key mechanism required for membrane proteostasis and cellular signaling. One of the intramembrane-cleaving proteases (I-CLiPs), γ-secretase, is also intimately implicated in Alzheimer's disease, a major neurodegenerative disease and leading cause of dementia. High-resolution crystal structural analyses have revealed that I-CLiPs harbor their active sites buried deeply in the membrane bilayer. Surprisingly, however, the key kinetic constants of these proteases, turnover number kcat and catalytic efficiency kcat/KM, are largely unknown. By investigating the kinetics of intramembrane cleavage of the Alzheimer's disease-associated β-amyloid precursor protein in vitro and in human embryonic kidney cells, we show that γ-secretase is a very slow protease with a kcat value similar to those determined recently for rhomboid-type I-CLiPs. Our results indicate that low turnover numbers may be a general feature of I-CLiPs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.