ArticleJournal of lipid research2013
PCSK9-mediated degradation of the LDL receptor generates a 17 kDa C-terminal LDL receptor fragment.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis.Journal of innate immunity · 2016Pooled it
- PCSK9 is a critical regulator of the innate immune response and septic shock outcome.Science translational medicine · 2014Trial
- Circulating cholesterol fuels SARS-CoV-2 replication via ORF3a.EMBO reports · 2026Article
- Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?International journal of molecular sciences · 2026Review
- Increased PCSK9 associated with cIMT in AS: A useful marker for subclinical atherosclerosis in patients with ankylosing spondylitis.Archives of rheumatology · 2024Article
- Review
- Synthetic Site-Specific Antibody-Ligand Conjugates Promote Asialoglycoprotein Receptor-Mediated Degradation of Extracellular Human PCSK9.ACS chemical biology · 2023Article
- Statins: a repurposed drug to fight cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness.Journal of clinical medicine · 2021Review
- The Pivotal Role of the Dysregulation of Cholesterol Homeostasis in Cancer: Implications for Therapeutic Targets.Cancers · 2020Review
- Membrane Heterogeneity Controls Cellular Endocytic Trafficking.Frontiers in cell and developmental biology · 2020Review
- Impact of PCSK9 loss-of-function genotype on 1-year mortality and recurrent infection in sepsis survivors.EBioMedicine · 2018Article
- γ-Secretase Inhibition Lowers Plasma Triglyceride-Rich Lipoproteins by Stabilizing the LDL Receptor.Cell metabolism · 2018Article
- Studies of the autoinhibitory segment comprising residues 31-60 of the prodomain of PCSK9: Possible implications for the mechanism underlying gain-of-function mutations.Molecular genetics and metabolism reports · 2016Article
- Article
- Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain.PloS one · 2016Article
- Site-1 protease-activated formation of lysosomal targeting motifs is independent of the lipogenic transcription control.Journal of lipid research · 2015Article
- Internalized PCSK9 dissociates from recycling LDL receptors in PCSK9-resistant SV-589 fibroblasts.Journal of lipid research · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the LDL receptor (LDLR) at the cell surface and reroutes the internalized LDLR to intracellular degradation. In this study, we have shown that PCSK9-mediated degradation of the full-length 160 kDa LDLR generates a 17 kDa C-terminal LDLR fragment. This fragment was not generated from mutant LDLRs resistant to PCSK9-mediated degradation or when degradation was prevented by chemicals such as ammonium chloride or the cysteine cathepsin inhibitor E64d. The observation that the 17 kDa fragment was only detected when the cells were cultured in the presence of the γ-secretase inhibitor DAPT indicates that this 17 kDa fragment undergoes γ-secretase cleavage within the transmembrane domain. The failure to detect the complementary 143 kDa ectodomain fragment is likely to be due to its rapid degradation in the endosomal lumen. The 17 kDa C-terminal LDLR fragment was also generated from a Class 5 mutant LDLR undergoing intracellular degradation. Thus, one may speculate that an LDLR with bound PCSK9 and a Class 5 LDLR with bound LDL are degraded by a similar mechanism that could involve ectodomain cleavage in the endosome.
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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.