ArticleProceedings of the National Academy of Sciences of the United States of America2020
Hepatic neddylation targets and stabilizes electron transfer flavoproteins to facilitate fatty acid β-oxidation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 47 citations in OpenAlex.
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- UBA3 reduction sensitizes cancer cells to NAE inhibitors.Life science alliance · 2026Article
- Article
- Syn III participated in rTMS-modulated emotional rescue in the prefrontal cortex under simulated space composite environment.Molecular psychiatry · 2026Article
- Neddylation Targets and Stabilizes NLRP3 to Augment Inflammasome-Mediated Colitis and Mood Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hepatic KLF9 Deficiency Inhibits Dehydroepiandrosterone (DHEA)-Induced Polycystic Ovary Syndrome via Liver-Ovary Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neddylation related gene signature for prognostic biomarkers in colorectal cancer with integrated bioinformatics and experimental analysis.Discover oncology · 2025Article
- First report of neonatal-onset glutaric aciduria type II in the Iranian population caused by a novel deleterious ETFA variant.Orphanet journal of rare diseases · 2025Article
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
- The NAE1-mediated neddylation operates as an essential post-translational modification checkpoint for effector CD8Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Hepatocyte-derived Igκ promotes HCC progression by stabilizing electron transfer flavoprotein subunit α to facilitate fatty acid β-oxidation.Journal of experimental & clinical cancer research : CR · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway.Acta biochimica et biophysica Sinica · 2024Article
- HepaticiScience · 2023Article
- Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism.Cell metabolism · 2023Article
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
- Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation.Cell reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neddylation is a ubiquitination-like pathway that controls cell survival and proliferation by covalently conjugating NEDD8 to lysines in specific substrate proteins. However, the physiological role of neddylation in mammalian metabolism remains elusive, and no mitochondrial targets have been identified. Here, we report that mouse models with liver-specific deficiency of NEDD8 or ubiquitin-like modifier activating enzyme 3 (UBA3), the catalytic subunit of the NEDD8-activating enzyme, exhibit neonatal death with spontaneous fatty liver as well as hepatic cellular senescence. In particular, liver-specific UBA3 deficiency leads to systemic abnormalities similar to glutaric aciduria type II (GA-II), a rare autosomal recessive inherited fatty acid oxidation disorder resulting from defects in mitochondrial electron transfer flavoproteins (ETFs: ETFA and ETFB) or the corresponding ubiquinone oxidoreductase. Neddylation inhibition by various strategies results in decreased protein levels of ETFs in neonatal livers and embryonic hepatocytes. Hepatic neddylation also enhances ETF expression in adult mice and prevents fasting-induced steatosis and mortality. Interestingly, neddylation is active in hepatic mitochondria. ETFs are neddylation substrates, and neddylation stabilizes ETFs by inhibiting their ubiquitination and degradation. Moreover, certain mutations of ETFs found in GA-II patients hinder the neddylation of these substrates. Taken together, our results reveal substrates for neddylation and add insight into GA-II.
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.