ArticleMolecular biology of the cell2016
Perturbation of neddylation-dependent NF-κB responses in the intestinal epithelium drives apoptosis and inhibits resolution of mucosal inflammation.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- NEDD8 Promotes the Progression and Inflammation of Keratoconus by Increasing the Expression of YAP1.Investigative ophthalmology & visual science · 2026Article
- Neddylation Targets and Stabilizes NLRP3 to Augment Inflammasome-Mediated Colitis and Mood Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integration analysis of single-cell and spatial transcriptomics identifies prognostic genes associated with neddylation in colorectal cancer.Discover oncology · 2025Article
- HIV proviral transcription and infectivity are enhanced by neddylation.Journal of virology · 2025Article
- Article
- Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, sensitizes cancer cells to VSVΔ51 oncolytic virotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration.American journal of human genetics · 2023Article
- Neddylation Regulation of Immune Responses.Research (Washington, D.C.) · 2023Review
- Emerging role of protein modification in inflammatory bowel disease.Journal of Zhejiang University. Science. B · 2022Review
- The Cellular and Developmental Roles of Cullins, Neddylation, and the COP9 Signalosome inFrontiers in physiology · 2022Review
- Cardioprotective effect of MLN4924 on ameliorating autophagic flux impairment in myocardial ischemia-reperfusion injury by Sirt1.Redox biology · 2021Article
- The pivotal roles of neddylation pathway in immunoregulation.Immunity, inflammation and disease · 2020Review
- HucMSC-exosomes carrying miR-326 inhibit neddylation to relieve inflammatory bowel disease in mice.Clinical and translational medicine · 2020Article
- Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Hypoxia and Innate Immunity: Keeping Up with the HIFsters.Annual review of immunology · 2020Review
- TRAF6 neddylation drives inflammatory arthritis by increasing NF-κB activation.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Protein neddylation and its alterations in human cancers for targeted therapy.Cellular signalling · 2018Review
- A Central Role for Heme Oxygenase-1 in the Control of Intestinal Epithelial Chemokine Expression.Journal of innate immunity · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Recent work has revealed a central role for neddylation (the conjugation of a Nedd8-moiety to Cullin proteins) in the fine tuning of the NF-κB response (via Cullin-1). In the present study, we investigated the contribution of Cullin-1 neddylation and NF-κB signaling to mucosal inflammatory responses in vitro and in vivo. Initial in vitro studies using cultured intestinal epithelial cells revealed that the neddylation inhibitor MLN4924 prominently induces the deneddylation of Cullin-1. Parallel western blot, luciferase reporter and gene target assays identified MLN4924 as a potent inhibitor of intestinal epithelial NF-κB. Subsequent studies revealed that MLN4924 potently induces epithelial apoptosis but only in the presence of additional inflammatory stimuli. In vivo administration of MLN4924 (3 mg/kg/d) in a TNBS-induce colitis model significantly accentuated disease severity. Indeed, MLN4924 resulted in worsened clinical scores and increased mortality early in the inflammatory response. Histologic analysis of the colon revealed that neddylation inhibition results in increased tissue damage and significantly increased mucosal apoptosis as determined by TUNEL and cleaved caspase-3 staining, particularly prominent within the epithelium. Extensions of these studies revealed that ongoing inflammation is associated with significant loss of deneddylase-1 (SENP8) expresssion. These studies reveal that intact Cullin-1 neddylation is central to resolution of acute inflammation.
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Registered trials
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