ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Central role for endothelial human deneddylase-1/SENP8 in fine-tuning the vascular inflammatory response.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 50 citations in OpenAlex.
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- Neddylation blockade protects endothelial cells against inflammation and ischemia-reperfusion injuries.Cell communication and signaling : CCS · 2026Article
- NEDD8 Promotes the Progression and Inflammation of Keratoconus by Increasing the Expression of YAP1.Investigative ophthalmology & visual science · 2026Article
- NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.Essays in biochemistry · 2025Review
- Neutrophil extracellular traps aggravate neuronal apoptosis and neuroinflammation via neddylation after traumatic brain injury.Theranostics · 2025Article
- Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats.Mediators of inflammation · 2024Article
- The COP9 signalosome reduces neuroinflammation and attenuates ischemic neuronal stress in organotypic brain slice culture model.Cellular and molecular life sciences : CMLS · 2023Article
- Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation.Cell reports · 2023Article
- Emerging role of protein modification in inflammatory bowel disease.Journal of Zhejiang University. Science. B · 2022Review
- Spatially Targeted Proteomics of the Host-Pathogen Interface during Staphylococcal Abscess Formation.ACS infectious diseases · 2021Article
- Inhibition of HDAC6 Activity Protects Against Endothelial Dysfunction and AtherogenesisFrontiers in physiology · 2021Article
- The pivotal roles of neddylation pathway in immunoregulation.Immunity, inflammation and disease · 2020Review
- The COP9 Signalosome: A Multi-DUB Complex.Biomolecules · 2020Review
- Neddylation, an Emerging Mechanism Regulating Cardiac Development and Function.Frontiers in physiology · 2020Review
- Role of the COP9 Signalosome (CSN) in Cardiovascular Diseases.Biomolecules · 2019Review
- TRAF6 neddylation drives inflammatory arthritis by increasing NF-κB activation.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Control and dysregulation of redox signalling in the gastrointestinal tract.Nature reviews. Gastroenterology & hepatology · 2019Review
- Astragaloside II alleviates the symptoms of experimental ulcerative colitisAmerican journal of translational research · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
A deeper understanding of the mechanisms that control responses to inflammation is critical to the development of effective therapies. We sought to define the most proximal regulators of the Cullin (Cul)-RING ligases, which play a central role in the stabilization of NF-κB and hypoxia-inducible factor (HIF). In these studies, we identify the human deneddylase-1 (SENP8) as a key regulator of Cul neddylation response in vitro and in vivo. Using human microvascular endothelial cells (HMECs), we examined inflammatory responses to LPS or TNF-α by assessing Cul neddylation status, NF-κB and HIF-1α stabilization, and inflammatory cytokine secretion. HMECs with an intact neddylation pathway showed a time-dependent induction of Cul-1 neddylation, nuclear translocation of NF-κB, stabilization of HIF-1α, and increased NF-κB/HIF-α promoter activity in response to LPS. HMECs lacking SENP8 were unable to neddylate Cul-1 and subsequently were unable to activate NF-κB or HIF-1α. Pharmacological targeting of neddylation (MLN4924) significantly abrogated NF-κB responses, induced HIF-1α promoter activity, and reduced secretion of TNF-α-elicited proinflammatory cytokines. MLN4924 stabilized HIF and abrogated proinflammatory responses while maintaining anti-inflammatory IL-10 responses in vivo following LPS administration. These studies identify SENP8 as a proximal regulator of Cul neddylation and provide an important role for SENP8 in fine-tuning the inflammatory response. Moreover, our findings provide feasibility for therapeutic targeting of the Culs during inflammation.
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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.