ArticleCell death and differentiation2018
Inhibition of neddylation by MLN4924 improves neointimal hyperplasia and promotes apoptosis of vascular smooth muscle cells through p53 and p62.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- 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
- Distinct types of protein modifications in diabetic endothelial dysfunction.Cardiovascular diabetology · 2025Review
- Blockade of neddylation through targeted inhibition of DCN1 alleviates renal fibrosis.Clinical science (London, England : 1979) · 2025Article
- RBM15 Protects From Myocardial Infarction by Stabilizing NAE1.JACC. Basic to translational science · 2024Article
- Integrated analysis reveals the regulatory mechanism of the neddylation inhibitor MLN4924 on the metabolic dysregulation in rabbit granulosa cells.BMC genomics · 2024Article
- Article
- Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis.Signal transduction and targeted therapy · 2024Article
- FOXO1-regulated lncRNA CYP1B1-AS1 suppresses breast cancer cell proliferation by inhibiting neddylation.Breast cancer research and treatment · 2023Article
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Experimental Liver Cirrhosis Inhibits Restenosis after Balloon Angioplasty.International journal of molecular sciences · 2023Article
- MLN4924 Promotes Self-Renewal of Limbal Stem Cells and Ocular Surface Restoration.Journal of personalized medicine · 2023Article
- Article
- p62 Promotes the Mitochondrial Localization of p53 through Its UBA Domain and Participates in Regulating the Sensitivity of Ovarian Cancer Cells to Cisplatin.International journal of molecular sciences · 2022Article
- Cardioprotective effect of MLN4924 on ameliorating autophagic flux impairment in myocardial ischemia-reperfusion injury by Sirt1.Redox biology · 2021Article
- Recent advances in cellular effects of fluoride: an update on its signalling pathway and targeted therapeutic approaches.Molecular biology reports · 2021Review
- Exosomes are involved in total body irradiation-induced intestinal injury in mice.Acta pharmacologica Sinica · 2021Article
- The regulatory roles of p53 in cardiovascular health and disease.Cellular and molecular life sciences : CMLS · 2021Review
- The Effect of Neddylation Blockade on Slug-Dependent Cancer Cell Migration Is Regulated by p53 Mutation Status.Cancers · 2021Article
- Neddylation, an Emerging Mechanism Regulating Cardiac Development and Function.Frontiers in physiology · 2020Review
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting apoptosis of vascular smooth muscle cells (VSMCs) represents an attractive approach to diminish the occurrence of restenosis. Neddylation is a highly conserved post-translational modification process and inhibition of neddylation has been shown to regulate apoptosis of other cells. However, the impacts of neddylation inhibition on VSMCs and neointimal hyperplasia have not been studied. In our present study, we have shown that MLN4924, a selective inhibitor of NEDD8-activating enzyme (NAE), markedly inhibited neointimal hyperplasia and accumulation of VSMCs, whereas increased apoptosis in the vascular wall. In vitro studies revealed that MLN4924 induced G2/M arrest and apoptosis of human VSMCs. Knockdown of NAE1 had similar effects. MLN4924 upregulated p53 and p62 in human VSMCs. Knockdown of either p53 or p62 mitigated the impacts of MLN4924 on G2/M arrest and apoptosis. Moreover, p53 knockdown abolished MLN4924-induced upregulation of p62. Finally, smooth muscle p53 knockout mice were generated and subjected to femoral artery injury and MLN4924 treatment. Deficiency of p53 in smooth muscle blocked the effects of MLN4924 on neointimal hyperplasia and apoptosis. Together, our results revealed that neddylation inhibition induces apoptosis through p53 and p62 in VSMCs and improves neointimal hyperplasia mainly by promoting apoptosis through smooth muscle p53 in mice. These pre-clinical data provide strong translational implications for targeting restenosis by perturbation of neddylation using MLN4924.
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