ArticleNature communications2022
Hepatic neddylation deficiency triggers fatal liver injury via inducing NF-κB-inducing kinase in mice.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- E3 Ubiquitin Ligases in MASH-Associated Liver Fibrosis: Mechanisms and Therapeutic Opportunities.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Neddylation Targets and Stabilizes NLRP3 to Augment Inflammasome-Mediated Colitis and Mood Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of neddylation in colorectal cancer and its therapeutic potential.Discover oncology · 2025Review
- Mechanistic insights into post-translational modifications in hepatic fibrosis: pathogenic roles and therapeutic potentials.Journal of translational medicine · 2025Review
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Article
- Natural medicines for treating liver fibrosis by modulating post-translational modifications.Frontiers in pharmacology · 2025Review
- Neddylation drives myofibrillogenesis in the developing heart.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- NIK Is a Mediator of Inflammation and Intimal Hyperplasia in Endothelial Denudation-Induced Vascular Injury.International journal of molecular sciences · 2024Article
- Unconventional posttranslational modification in innate immunity.Cellular and molecular life sciences : CMLS · 2024Review
- The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.Biomolecules · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Chemical Evolution and Biological Evaluation of Natural Products for Efficient Therapy of Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- New insights into SUMOylation and NEDDylation in fibrosis.Frontiers in pharmacology · 2024Review
- Targeted Therapy of Acute Liver Injury via Cryptotanshinone-Loaded Biomimetic Nanoparticles Derived from Mesenchymal Stromal Cells Driven by Homing.Pharmaceutics · 2023Article
- Preventing acute liver injury via hepatocyte-targeting nano-antioxidants.Cell proliferation · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The conjugation of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) to target proteins, termed neddylation, participates in many cellular processes and is aberrant in various pathological diseases. Its relevance to liver function and failure remains poorly understood. Herein, we show dysregulated expression of NAE1, a regulatory subunit of the only NEDD8 E1 enzyme, in human acute liver failure. Embryonic- and adult-onset deletion of NAE1 in hepatocytes causes hepatocyte death, inflammation, and fibrosis, culminating in fatal liver injury in mice. Hepatic neddylation deficiency triggers oxidative stress, mitochondrial dysfunction, and hepatocyte reprogramming, potentiating liver injury. Importantly, NF-κB-inducing kinase (NIK), a serine/Thr kinase, is a neddylation substrate. Neddylation of NIK promotes its ubiquitination and degradation. Inhibition of neddylation conversely causes aberrant NIK activation, accentuating hepatocyte damage and inflammation. Administration of N-acetylcysteine, a glutathione surrogate and antioxidant, mitigates liver failure caused by hepatic NAE1 deletion in adult male mice. Therefore, hepatic neddylation is important in maintaining postnatal and adult liver homeostasis, and the identified neddylation targets/pathways provide insights into therapeutically intervening acute liver failure.
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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.