ArticleJournal of lipid research2012
Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR.
Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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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.
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Who cites it
55 citing papers in PubMed, 111 citations in OpenAlex.
- Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody.Circulation. Cardiovascular genetics · 2015Trial
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9): The Multifaceted Biology, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Safety, Pharmacokinetics, Translational and Molecular Mechanistic Insights on the Prostate Cancer Recurrence Suppressor Pseurotin A.Molecules (Basel, Switzerland) · 2025Article
- PCSK9-promoted LDLR degradation: Recruitment or prevention of essential cofactors?Metabolism open · 2025Article
- Emerging roles of PCSK9 in kidney disease: lipid metabolism, megalin regulation and proteinuria.Pflugers Archiv : European journal of physiology · 2025Review
- EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis.Cell metabolism · 2025Article
- Pathways and Molecular Mechanisms Governing LDL Receptor Regulation.Circulation research · 2025Review
- Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening.Atherosclerosis · 2025Article
- Unraveling Estrogen and PCSK9's Roles in Lipid Metabolism Disorders among Ovariectomized Mice.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Postprandial exercise regulates tissue-specific triglyceride uptake through angiopoietin-like proteins.JCI insight · 2024Article
- Repurposing an endogenous degradation domain for antibody-mediated disposal of cell-surface proteins.EMBO reports · 2024Article
- The LDL receptor is regulated by membrane cholesterol as revealed by fluorescence fluctuation analysis.Biophysical journal · 2023Article
- Delivery of low-density lipoprotein from endocytic carriers to mitochondria supports steroidogenesis.Nature cell biology · 2023Article
- Review
- RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels.Circulation research · 2023Article
- Lowering low-density lipoprotein cholesterol: from mechanisms to therapies.Life metabolism · 2022Review
- Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance.Nature communications · 2022Article
- Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors.Cancers · 2021Article
- The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells.Foods (Basel, Switzerland) · 2021Article
- Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that promotes degradation of cell surface LDL receptors (LDLRs) in selected cell types. Here we used genetic and pharmacological inhibitors to define the pathways involved in PCSK9-mediated LDLR degradation. Inactivating mutations in autosomal recessive hypercholesterolemia (ARH), an endocytic adaptor, blocked PCSK9-mediated LDLR degradation in lymphocytes but not in fibroblasts. Thus, ARH is not specifically required for PCSK9-mediated LDLR degradation. Knockdown of clathrin heavy chain with siRNAs prevented LDLR degradation. In contrast, prevention of ubiquitination of the LDLR cytoplasmic tail, inhibition of proteasomal activity, or disruption of proteins required for lysosomal targeting via macroautophagy (autophagy related 5 and 7) or the endosomal sorting complex required for trafficking (ESCRT) pathway (hepatocyte growth factor-regulated Tyr-kinase substrate and tumor suppressor gene 101) failed to block PCSK9-mediated LDLR degradation. These findings are consistent with a model in which the LDLR-PCSK9 complex is internalized via clathrin-mediated endocytosis and then routed to lysosomes via a mechanism that does not require ubiquitination and is distinct from the autophagy and proteosomal degradation pathways. Finally, the PCSK9-LDLR complex appears not to be transported by the canonical ESCRT pathway.
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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.