ArticleThe Journal of biological chemistry2018
Loss-of-function PCSK9 mutants evade the unfolded protein response sensor GRP78 and fail to induce endoplasmic reticulum stress when retained.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation.Life (Basel, Switzerland) · 2025Article
- Efficient prime editing in mouse brain, liver and heart with dual AAVs.Nature biotechnology · 2024Article
- A Metabolic Enhancer Protects against Diet-Induced Obesity and Liver Steatosis and Corrects a Pro-Atherogenic Serum Profile in Mice.Nutrients · 2023Article
- Surf4, cargo trafficking, lipid metabolism, and therapeutic implications.Journal of molecular cell biology · 2023Review
- Expanding Biology of PCSK9: Roles in Atherosclerosis and Beyond.Current atherosclerosis reports · 2022Review
- The Emerging Roles of Intracellular PCSK9 and Their Implications in Endoplasmic Reticulum Stress and Metabolic Diseases.Metabolites · 2022Review
- PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology.Biomedicines · 2021Review
- Construction of point mutation rabbits using CRISPR/Cas9.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Article
- The loss-of-function PCSK9Q152H variant increases ER chaperones GRP78 and GRP94 and protects against liver injury.The Journal of clinical investigation · 2021Article
- Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications.Frontiers in cardiovascular medicine · 2021Review
- Proteostasis Regulation in the Endoplasmic Reticulum: An Emerging Theme in the Molecular Pathology and Therapeutic Management of Familial Hypercholesterolemia.Frontiers in genetics · 2020Review
- Article
- The role and therapeutic potential of heat shock proteins in haemorrhagic stroke.Journal of cellular and molecular medicine · 2019Review
- GDF10 blocks hepatic PPARγ activation to protect against diet-induced liver injury.Molecular metabolism · 2019Article
- Diet-induced hepatic steatosis abrogates cell-surface LDLR by inducingThe Journal of biological chemistry · 2019Article
- Proprotein convertase subtilisin/kexin type 9 and lipid metabolism.Current opinion in lipidology · 2019Review
- Novel strategies to target proprotein convertase subtilisin kexin 9: beyond monoclonal antibodies.Cardiovascular research · 2019Review
- The trypan blue cellular debris assay: a novel low-cost method for the rapid quantification of cell death.MethodsX · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The proprotein convertase subtilisin/kexin type-9 (PCSK9) plays a central role in cardiovascular disease (CVD) by degrading hepatic low-density lipoprotein receptor (LDLR). As such, loss-of-function (LOF) PCSK9 variants that fail to exit the endoplasmic reticulum (ER) increase hepatic LDLR levels and lower the risk of developing CVD. The retention of misfolded protein in the ER can cause ER stress and activate the unfolded protein response (UPR). In this study, we investigated whether a variety of LOF PCSK9 variants that are retained in the ER can cause ER stress and hepatic cytotoxicity. Although overexpression of these PCSK9 variants caused an accumulation in the ER of hepatocytes, UPR activation or apoptosis was not observed. Furthermore, ER retention of endogenous PCSK9 via splice switching also failed to induce the UPR. Consistent with these
Indexed as
Identifiers
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.