ArticleCell reports2016
Activation of CDK4 Triggers Development of Non-alcoholic Fatty Liver Disease.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 45 citations in OpenAlex.
- Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.Nature aging · 2026Article
- [Research progress on cellular senescence and liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- The Non-Canonical ChREBPα Activity Suppresses the Activation of Hepatic Stellate Cells and Liver Fibrosis by Antagonizing TGF-β-E2F1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring drug repurposing as a therapeutic strategy for non-alcoholic fatty liver disease (NAFLD): identification of potential targets and pathways.Gastroenterology and hepatology from bed to bench · 2025Article
- Hepatocyte-specific angiotensinogen deficiency inhibits Western diet-induced liver steatosis with suppression of cell division in mice.Global translational medicine · 2025Article
- Distinct Lipidomic Profiles between People Living with HIV Treated with E/C/F/TAF or B/F/TAF: An Open-Label Prospective Cohort Study.Infectious diseases and therapy · 2024Article
- Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring.Cellular and molecular gastroenterology and hepatology · 2024Article
- Aging and aging-related diseases: from molecular mechanisms to interventions and treatments.Signal transduction and targeted therapy · 2022Review
- Polyploidization of Hepatocytes: Insights into the Pathogenesis of Liver Diseases.Biomolecules & therapeutics · 2022Review
- Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).Signal transduction and targeted therapy · 2022Review
- Palbociclib regulates intracellular lipids in mammary tumor cells by secreting lipoprotein lipase.Pharmacological reports : PR · 2022Article
- Modulation of Oxidative Stress-Induced Senescence during Non-Alcoholic Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Clinical implications and molecular mechanisms of Cyclin-dependent kinases 4 for patients with hepatocellular carcinoma.BMC gastroenterology · 2022Article
- TTC39B destabilizes retinoblastoma protein promoting hepatic lipogenesis in a sex-specific fashion.Journal of hepatology · 2022Article
- CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.Research (Washington, D.C.) · 2022Review
- Aging Induces Hepatic Oxidative Stress and Nuclear Proteomic Remodeling in Liver from Wistar Rats.Antioxidants (Basel, Switzerland) · 2021Article
- Evaluating causality of cellular senescence in non-alcoholic fatty liver disease.JHEP reports : innovation in hepatology · 2021Review
- DHA Suppresses Hepatic Lipid AccumulationFrontiers in nutrition · 2021Article
- Pluripotent Stem Cell-Derived Hepatocytes Phenotypic Screening Reveals Small Molecules Targeting the CDK2/4-C/EBPα/DGAT2 Pathway Preventing ER-Stress Induced Lipid Accumulation.International journal of molecular sciences · 2020Article
- CDKN2A/p16INK4a suppresses hepatic fatty acid oxidation through the AMPKα2-SIRT1-PPARα signaling pathway.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The development of non-alcoholic fatty liver disease (NAFLD) is a multiple step process. Here, we show that activation of cdk4 triggers the development of NAFLD. We found that cdk4 protein levels are elevated in mouse models of NAFLD and in patients with fatty livers. This increase leads to C/EBPα phosphorylation on Ser193 and formation of C/EBPα-p300 complexes, resulting in hepatic steatosis, fibrosis, and hepatocellular carcinoma (HCC). The disruption of this pathway in cdk4-resistant C/EBPα-S193A mice dramatically reduces development of high-fat diet (HFD)-mediated NAFLD. In addition, inhibition of cdk4 by flavopiridol or PD-0332991 significantly reduces development of hepatic steatosis, the first step of NAFLD. Thus, this study reveals that activation of cdk4 triggers NAFLD and that inhibitors of cdk4 may be used for the prevention/treatment of NAFLD.
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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.