ArticleThe Journal of biological chemistry2013
Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2).
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 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- Effects of Statin Therapy on Plasma Proprotein Convertase Subtilisin/kexin Type 9 and Sortilin Levels in Statin-Naive Patients with Coronary Artery Disease.Journal of atherosclerosis and thrombosis · 2016Trial
- Recent advances in function-enhanced antibody-drug conjugates: Antibody optimization and payload combination.Acta pharmacologica Sinica · 2026Article
- The Roles of PCSK9 in Alzheimer's Disease: A Systematic Review of Clinical, Genetic, and Preclinical Evidence.Life (Basel, Switzerland) · 2025Review
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Exploring the next generation of antibody-drug conjugates.Nature reviews. Clinical oncology · 2024Review
- Repurposing an endogenous degradation domain for antibody-mediated disposal of cell-surface proteins.EMBO reports · 2024Article
- Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: a prospective study.Scientific reports · 2023Article
- Heparin Does Not Regulate Circulating Human PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) in a General Population-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- PCSK9 deficiency alters brain lipid composition without affecting brain development and function.Frontiers in molecular neuroscience · 2022Article
- Targeting PCSK9: a promising adjuvant strategy in cancer immunotherapy.Signal transduction and targeted therapy · 2021Article
- Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications.Frontiers in cardiovascular medicine · 2021Review
- Hepatic Glucagon Signaling Regulates PCSK9 and Low-Density Lipoprotein Cholesterol.Circulation research · 2019Article
- Cell-associated heparin-like molecules modulate the ability of LDL to regulate PCSK9 uptake.Journal of lipid research · 2019Article
- PCSK9: From Basic Science Discoveries to Clinical Trials.Circulation research · 2018Review
- APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated degradation of the LDLR in vivo.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Article
- Physiological and therapeutic regulation of PCSK9 activity in cardiovascular disease.Basic research in cardiology · 2017Review
- PCSK9 targets important for lipid metabolism.Clinical research in cardiology supplements · 2017Review
- PCSK9 as a therapeutic target for cardiovascular disease.Experimental and therapeutic medicine · 2017Article
- Lowering serum lipids via PCSK9-targeting drugs: current advances and future perspectives.Acta pharmacologica Sinica · 2017Review
- Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain.PloS one · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low density lipoprotein receptor protein levels by diverting it to lysosomes. Monoclonal antibody therapeutics aimed to neutralize PCSK9 have been shown to successfully lower serum LDL levels; however, we previously found that such therapeutic antibodies are subject to PCSK9-mediated clearance. In this study, we discovered that PCSK9 interacts via its C-terminal domain directly and in a pH-dependent manner with amyloid precursor protein as well as its closely related family member, amyloid precursor protein-like protein 2. Furthermore, we determined that amyloid precursor protein-like protein-2, but not amyloid precursor protein, is involved in mediating postendocytic delivery of PCSK9 to lysosomes and is therefore important for PCSK9 function. Based on our data, we propose a model for a lysosomal transport complex by which a soluble protein can target another protein for degradation from the luminal side of the membrane by bridging it to a lysosomally targeted transmembrane protein.
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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 OpenQuestion graph.