ArticleProceedings of the National Academy of Sciences of the United States of America2018
Neddylation mediates ventricular chamber maturation through repression of Hippo signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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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
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Rethinking Left Ventricular Noncompaction and Excessive Left Ventricular Trabeculation: Development, Genetics, and a Proposed Conceptual Framework.Journal of clinical medicine · 2026Review
- Reduced dosage of Kmt2d modifies Tbx1 haploinsufficiency toward phenotypes of 22q11.2DS.JCI insight · 2026Article
- [Research progress on the regulatory role and mechanisms of the Hippo signaling pathway in the pathogenesis of congenital heart disease].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Review
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- COP9 signalosome deneddylation activity is required for proliferation but not dedifferentiation of vascular smooth muscle cells in neointimal hyperplasia.American journal of physiology. Heart and circulatory physiology · 2026Article
- Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.Molecular and cellular biochemistry · 2026Review
- CUL7-mediated KEAP1 ubiquitination promotes the progression of colon cancer via NRF2 signaling.Cell death & disease · 2026Article
- NEDD8 Promotes the Progression and Inflammation of Keratoconus by Increasing the Expression of YAP1.Investigative ophthalmology & visual science · 2026Article
- Article
- Neddylation E1 Obligatory Subunit Nae1 Is Critical to Neuromuscular Junction Development and Maintenance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- New Types of Post-Translational Modification of Proteins in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- The effects of YAP/TAZ in cardiomyocytes: a scoping review.Molecular biology reports · 2025Article
- Hippo in smooth muscle - a therapeutic target in vascular diseases driven by aging and hypertension.Frontiers in physiology · 2025Review
- Neddylation drives myofibrillogenesis in the developing heart.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Inhibition of cardiomyocyte neddylation impairs embryonic cardiac morphogenesis.Journal of molecular and cellular cardiology · 2024Article
- Quantitative proteomics reveals cellular responses to individual mAb expression and tunicamycin in CHO cells.Applied microbiology and biotechnology · 2024Article
- Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination.Science advances · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
During development, ventricular chamber maturation is a crucial step in the formation of a functionally competent postnatal heart. Defects in this process can lead to left ventricular noncompaction cardiomyopathy and heart failure. However, molecular mechanisms underlying ventricular chamber development remain incompletely understood. Neddylation is a posttranslational modification that attaches ubiquitin-like protein NEDD8 to protein targets via NEDD8-specific E1-E2-E3 enzymes. Here, we report that neddylation is temporally regulated in the heart and plays a key role in cardiac development. Cardiomyocyte-specific knockout of NAE1, a subunit of the E1 neddylation activating enzyme, significantly decreased neddylated proteins in the heart. Mice lacking NAE1 developed myocardial hypoplasia, ventricular noncompaction, and heart failure at late gestation, which led to perinatal lethality. NAE1 deletion resulted in dysregulation of cell cycle-regulatory genes and blockade of cardiomyocyte proliferation in vivo and in vitro, which was accompanied by the accumulation of the Hippo kinases Mst1 and LATS1/2 and the inactivation of the YAP pathway. Furthermore, reactivation of YAP signaling in NAE1-inactivated cardiomyocytes restored cell proliferation, and YAP-deficient hearts displayed a noncompaction phenotype, supporting an important role of Hippo-YAP signaling in NAE1-depleted hearts. Mechanistically, we found that neddylation regulates Mst1 and LATS2 degradation and that Cullin 7, a NEDD8 substrate, acts as the ubiquitin ligase of Mst1 to enable YAP signaling and cardiomyocyte proliferation. Together, these findings demonstrate a role for neddylation in heart development and, more specifically, in the maturation of ventricular chambers and also identify the NEDD8 substrate Cullin 7 as a regulator of Hippo-YAP signaling.
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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.