ArticleEuropean heart journal2020
Cyclase-associated protein 1 is a binding partner of proprotein convertase subtilisin/kexin type-9 and is required for the degradation of low-density lipoprotein receptors by proprotein convertase subtilisin/kexin type-9.
Article in European heart journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Multiomic integration analysis identifies atherogenic metabolites mediating between novel immune genes and cardiovascular risk.Genome medicine · 2024Pooled it
- A PD-L1 Nanobody-Engineered Synthetic RNA Virus Enhances Hepatocellular Carcinoma Immunotherapy by Interfering PCSK9 and Upregulating MHC-I.Exploration (Beijing, China) · 2026Article
- The Impact of PCSK9 Inhibitors on Circulatory Inflammation: Mechanisms, Evidence, and Application Prospects.JACC. Asia · 2026Review
- PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026Review
- Review: natural compounds as PCSK9 inhibitors for antiviral therapy.Archives of microbiology · 2026Review
- Type II alveolar epithelial cell-specific CAP1 loss is associated with spontaneous pulmonary fibrosis and altered complement 5 signaling.BMC pulmonary medicine · 2026Article
- LDL receptor-independent mechanisms of proprotein convertase subtilisin/kexin type 9 in cardiovascular pathophysiology.Frontiers in cardiovascular medicine · 2026Review
- PCSK9 Loss-of-Function Disrupts Cellular Microfilament Network via LIN28A/HES5/JMY Axis in Neural Tube Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transcriptome alterations underlying metabolic dysfunction and liver disease in myotonic dystrophy type 1.Human molecular genetics · 2025Article
- The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications.Biomolecules · 2025Review
- The value of CD47 and CAP1 levels in early diagnosis and MACE prediction for patients with non-ST-segment elevation myocardial infarction.BMC cardiovascular disorders · 2025Article
- PCSK9 deficiency promotes the development of peripheral neuropathy.JCI insight · 2025Article
- PCSK9 and its relationship with HMGB1, TLR4, and TNFα in non-statin and statin-treated coronary artery disease patients.Molecular and cellular biochemistry · 2025Article
- CAP1: a novel extracellular vesicle marker linked to endothelial senescence in atherosclerosis.Biology direct · 2025Article
- Novel RNA-Based Therapies in the Management of Dyslipidemias.International journal of molecular sciences · 2025Review
- PCSK9 in T-cell function and the immune response.Biomarker research · 2024Review
- The importance of paying attention to the role of lipid-lowering drugs in controlling dengue virus infection.Virology journal · 2024Review
- PCSK9 Inhibitors: Focus on Evolocumab and Its Impact on Atherosclerosis Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets.Chinese journal of integrative medicine · 2024Review
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsProprotein convertase subtilisin/kexin type-9 (PCSK9), a molecular determinant of low-density lipoprotein (LDL) receptor (LDLR) fate, has emerged as a promising therapeutic target for atherosclerotic cardiovascular diseases. However, the precise mechanism by which PCSK9 regulates the internalization and lysosomal degradation of LDLR is unknown. Recently, we identified adenylyl cyclase-associated protein 1 (CAP1) as a receptor for human resistin whose globular C-terminus is structurally similar to the C-terminal cysteine-rich domain (CRD) of PCSK9. Herein, we investigated the role of CAP1 in PCSK9-mediated lysosomal degradation of LDLR and plasma LDL cholesterol (LDL-C) levels. METHODS AND
resultsThe direct binding between PCSK9 and CAP1 was confirmed by immunoprecipitation assay, far-western blot, biomolecular fluorescence complementation, and surface plasmon resonance assay. Fine mapping revealed that the CRD of PCSK9 binds with the Src homology 3 binding domain (SH3BD) of CAP1. Two loss-of-function polymorphisms found in human PCSK9 (S668R and G670E in CRD) were attributed to a defective interaction with CAP1. siRNA against CAP1 reduced the PCSK9-mediated degradation of LDLR in vitro. We generated CAP1 knock-out mice and found that the viable heterozygous CAP1 knock-out mice had higher protein levels of LDLR and lower LDL-C levels in the liver and plasma, respectively, than the control mice. Mechanistic analysis revealed that PCSK9-induced endocytosis and lysosomal degradation of LDLR were mediated by caveolin but not by clathrin, and they were dependent on binding between CAP1 and caveolin-1.
conclusionWe identified CAP1 as a new binding partner of PCSK9 and a key mediator of caveolae-dependent endocytosis and lysosomal degradation of LDLR.
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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.