ArticleJCI insight2017
E2F1 inhibits circulating cholesterol clearance by regulating Pcsk9 expression in the liver.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Hepatocyte-specific yes-associated protein knockout exacerbates non-alcoholic steatohepatitis by upregulating PCSK9.Journal of gastroenterology · 2026Article
- Methionine Metabolism Dictates PCSK9 Expression and Antitumor Potency of PD-1 Blockade in MSS Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations.Frontiers in pharmacology · 2024Review
- Article
- The cholesterol uptake regulator PCSK9 promotes and is a therapeutic target in APC/KRAS-mutant colorectal cancer.Nature communications · 2022Article
- Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats.International journal of molecular sciences · 2022Article
- Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development.Gastroenterology · 2022Article
- The Emerging Roles of Intracellular PCSK9 and Their Implications in Endoplasmic Reticulum Stress and Metabolic Diseases.Metabolites · 2022Review
- RNA Sequencing Analysis of Gene Expression by Electroacupuncture in Guinea Pig Gallstone Models.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Article
- GWAS in Africans identifies novel lipids loci and demonstrates heterogenous association within Africa.Human molecular genetics · 2021Article
- The cholesterol esterification inhibitor avasimibe suppresses tumour proliferation and metastasis via the E2F-1 signalling pathway in prostate cancer.Cancer cell international · 2021Article
- Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle.International journal of molecular sciences · 2021Article
- Methyl Ferulic Acid Attenuates Human Cardiac Fibroblasts Differentiation and Myocardial Fibrosis by Suppressing pRB-E2F1/CCNE2 and RhoA/ROCK2 Pathway.Frontiers in pharmacology · 2021Article
- Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications.Frontiers in cardiovascular medicine · 2021Review
- Transcriptional E2F1/2/3/6 as potential prognostic biomarkers in cutaneous melanoma.American journal of translational research · 2021Article
- Characterization of the CDAA Diet-Induced Non-alcoholic Steatohepatitis Model: Sex-Specific Differences in Inflammation, Fibrosis, and Cholesterol Metabolism in Middle-Aged Mice.Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholesterol accumulation in the liver is an early event in nonalcoholic fatty liver disease (NAFLD). Here, we demonstrate that E2F1 plays a crucial role in maintaining cellular cholesterol homeostasis by regulating cholesterol uptake via proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme that promotes low-density lipoprotein receptor (LDLR) degradation upon activation. E2f1-/- mice display reduced total plasma cholesterol levels and increased cholesterol content in the liver. In this study, we show that E2f1 deletion in cellular and mouse models leads to a marked decrease in Pcsk9 expression and an increase in LDLR expression. In addition to the upregulation of LDLR, we report that E2f1-/- hepatocytes exhibit increased LDL uptake. ChIP-Seq and PCSK9 promoter reporter experiments confirmed that E2F1 binds to and transactivates the PCSK9 promoter. Interestingly, E2f1-/- mice fed a high-cholesterol diet (HCD) display a fatty liver phenotype and liver fibrosis, which is reversed by reexpression of PCSK9 in the liver. Collectively, these data indicate that E2F1 regulates cholesterol uptake and that the loss of E2F1 leads to abnormal cholesterol accumulation in the liver and the development of fibrosis in response to an HCD.
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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.