ArticleThe Journal of biological chemistry2013
Systematic proteomic analysis identifies β-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic β-cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 88 citations in OpenAlex.
- BACE2 tunes lipid uptake through lipid transporters shedding supporting cancer cell proliferation.Journal of experimental & clinical cancer research : CR · 2026Article
- Elenbecestat and Compound 89 Potently Inhibit BACE1 but Not BACE2 When Subchronically Dosed in Non-Human Primates.Proteomics · 2026Article
- BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions.EMBO reports · 2026Article
- Sez6L2 autoimmunity induces cerebellar ataxia in mice.Journal of neuroinflammation · 2025Article
- Charting γ-secretase substrates by explainable AI.Nature communications · 2025Article
- ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism.Journal of molecular cell biology · 2025Article
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.The Journal of clinical investigation · 2024Article
- Unveiling the mechanistic link between extracellular amyloid fibrils, mechano-signaling and YAP activation in cancer.Cell death & disease · 2024Article
- The Alzheimer's disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130.Molecular neurodegeneration · 2023Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- Characterization of the Secretome, Transcriptome, and Proteome of Human β Cell Line EndoC-βH1.Molecular & cellular proteomics : MCP · 2022Article
- PTPRD and DCC Are Novel BACE1 Substrates Differentially Expressed in Alzheimer's Disease: A Data Mining and Bioinformatics Study.International journal of molecular sciences · 2022Article
- The β-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice.Molecular neurobiology · 2022Article
- The case for low-level BACE1 inhibition for the prevention of Alzheimer disease.Nature reviews. Neurology · 2021Review
- BACE2 suppression in mice aggravates the adverse metabolic consequences of an obesogenic diet.Molecular metabolism · 2021Article
- BACE1 Inhibition Increases Susceptibility to Oxidative Stress by Promoting Mitochondrial Damage.Antioxidants (Basel, Switzerland) · 2021Article
- The emerging role of β-secretases in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Is It the Twilight of BACE1 Inhibitors?Current neuropharmacology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expansion of functional islet β-cell mass is a physiological process to compensate for increased insulin demand. Deficiency or pharmacological inhibition of the plasma membrane protease BACE2 enhances pancreatic β-cell function and proliferation, and therefore BACE2 is a putative target for the therapeutic intervention under conditions of β-cell loss and dysfunction. To gain a molecular understanding of BACE2 function, we performed a systematic and quantitative proteomic analysis to map the natural substrate repertoire of BACE2 and its homologue BACE1 in β-cells. Loss- and gain-of-function studies of in vitro and in vivo models identified specific and functionally heterogeneous targets. Our analysis revealed non-redundant roles of BACE1/2 in ectodomain shedding with BACE1 regulating a broader and BACE2 a more distinct set of β-cell-enriched substrates including two proteins of the seizure 6 protein family (SEZ6L and SEZ6L2). Lastly, our study provides insights into the global β-cell sheddome and secretome, an important prerequisite to uncover novel mechanisms contributing to β-cell homeostasis and a resource for therapeutic target and biomarker discoveries.
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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 Socratic graph.