ArticleProceedings of the National Academy of Sciences of the United States of America2024
Cullin 3 RING E3 ligase inactivation causes NRF2-dependent NADH reductive stress, hepatic lipodystrophy, and systemic insulin resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- A Selective Cullin 3 RING E3 Ligase Inhibitor Attenuates Hyperglycemia via Dual Insulin Sensitizing and Insulinotropic Action.Diabetes · 2026Article
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- The inner nuclear membrane protein SUN1 regulates cullin-3 neddylation to maintain insulin signaling.bioRxiv : the preprint server for biology · 2026Article
- BRD4 modulates antimicrobial defense via non-canonical NRF2 activation in macrophages to confer protection against sepsis.PLoS pathogens · 2026Article
- A genetically encoded bifunctional enzyme mitigates redox imbalance and lipotoxicity.Nature metabolism · 2026Article
- DDIT3 drives nucleus pulposus cell PANoptosis and intervertebral disc degeneration progression.Apoptosis : an international journal on programmed cell death · 2026Article
- SLC25A11-mediated reprogramming of mitochondrial redox state and lipid peroxidation confers NRF2-dependent ferroptosis resistance in biliary tract cancer.Cellular & molecular biology letters · 2026Article
- Atypical endocrine manifestations in Gordon syndrome caused by CUL3 mutation: a case report.Frontiers in medicine · 2026Article
- Liver reprogramming toward hepatocellular carcinoma following hepatitis C sustained virologic response: a narrative review.Translational gastroenterology and hepatology · 2026Review
- Adipose cullin 3 mediates the antiobesity effect of pan neddylation inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- NRF2 Dysregulation and Therapeutic Insights Across Chronic Kidney Diseases.International journal of molecular sciences · 2025Review
- Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.The EMBO journal · 2025Review
- Reductive stress-a common metabolic feature of obesity and cancer.Acta pharmaceutica Sinica. B · 2024Review
- Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function.Antioxidants (Basel, Switzerland) · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Cullin RING E3 ligases (CRL) have emerged as key regulators of disease-modifying pathways and therapeutic targets. Cullin3 (Cul3)-containing CRL (CRL3) has been implicated in regulating hepatic insulin and oxidative stress signaling. However, CRL3 function in liver pathophysiology is poorly defined. Here, we report that hepatocyte Cul3 knockout results in rapid resolution of steatosis in obese mice. However, the remarkable resistance of hepatocyte Cul3 knockout mice to developing steatosis does not lead to overall metabolic improvement but causes systemic metabolic disturbances. Liver transcriptomics analysis identifies that CRL3 inactivation causes persistent activation of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant defense pathway, which also reprograms the lipid transcriptional network to prevent TG storage. Furthermore, global metabolomics reveals that NRF2 activation induces numerous NAD
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