ReviewAntioxidants & redox signaling2014
Targeting Neddylation pathways to inactivate cullin-RING ligases for anticancer therapy.
Review in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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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
141 citing papers in PubMed, 241 citations in OpenAlex.
- ABTB1, as an E3 ubiquitin ligase, suppresses Th17 cell differentiation and mitigates autoimmune inflammation by promoting STAT3 ubiquitination and degradation.Cellular & molecular immunology · 2026Article
- 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
- Overcoming Resistance in Triple-Negative Breast Cancer: A Translational Perspective on Next-Generation DNA Damage Response Inhibitors and Synthetic Lethality.Molecules (Basel, Switzerland) · 2026Review
- UBE2M deficiency in alveolar macrophages promotes emphysema through HIF-2α/MMP12 axis.Chinese medical journal pulmonary and critical care medicine · 2026Article
- Neddylation relieves cytoskeletal tension to permit primary cilia formation during mouse decidualization.Cell communication and signaling : CCS · 2026Article
- SIRT1 reduced DDX5 neddylation to attenuate myocardial ischemia/reperfusion injury.Human cell · 2026Article
- Integration analysis of single-cell and spatial transcriptomics identifies prognostic genes associated with neddylation in colorectal cancer.Discover oncology · 2025Article
- Epithelial‑mesenchymal plasticity and cisplatin resistance in germ cell tumors: Mechanisms and emerging therapeutic strategies (Review).International journal of oncology · 2025Review
- The neddylation of the RNA-dependent RNA polymerase 3D of Coxsackievirus B3 promotes viral replication.Journal of virology · 2025Article
- Pharmacological inhibition of Epac1 protects against pulmonary fibrosis by blocking FoxO3a neddylation.The European respiratory journal · 2025Article
- Protein neddylation in lung tumorigenesis: Target validation and targeted therapy.Fundamental research · 2025Review
- PRMT1-mediated methylation of UBE2m promoting calcium oxalate crystal-induced kidney injury by inhibiting fatty acid metabolism.Cell death & disease · 2025Article
- SUMOylation of the lysine-less tumor suppressor p14ARF counters ubiquitylation-dependent degradation.Cell death & disease · 2025Article
- NEDDylation Regulates CD8+ T-cell Metabolism and Antitumor Immunity.Cancer immunology research · 2025Article
- Neddylation of RhoA impairs its protein degradation and promotes renal interstitial fibrosis progression in diabetic nephropathy.Acta pharmacologica Sinica · 2025Article
- MLN4924 suppresses tumor metabolism and growth of clear cell renal cell carcinoma by stabilizing nuclear FBP1.Cell death discovery · 2025Article
- Pan-cancer analysis unveils the role and mechanisms of neddylation modifications in tumorigenesis.Medical oncology (Northwood, London, England) · 2025Article
- Blockade of neddylation through targeted inhibition of DCN1 alleviates renal fibrosis.Clinical science (London, England : 1979) · 2025Article
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
significanceProtein neddylation is catalyzed by an E1 NEDD8-activating enzyme (NAE), an E2 NEDD8-conjugating enzyme, and an E3 NEDD8 ligase. Known physiological substrates of neddylation are cullin family members. Cullin neddylation leads to activation of cullin-RING ligases (CRLs), the largest family of E3 ubiquitin ligases responsible for ubiquitylation and degradation of many key signaling/regulatory proteins. Thus, through modulating CRLs, neddylation regulates many biological processes, including cell cycle progression, signal transduction, and tumorigenesis. Given that NEDD8 is overexpressed and CRLs are abnormally activated in many human cancers, targeting protein neddylation, in general, and cullin neddylation, in particular, appears to be an attractive anticancer approach. RECENT ADVANCES: MLN4924, a small molecule inhibitor of NAE, was discovered that inactivates CRLs and causes accumulation of CRL substrates to suppress tumor cell growth both in vitro and in vivo. Promising preclinical results advanced MLN4924 to several clinical trials for anticancer therapy. CRITICAL ISSUES: In preclinical settings, MLN4924 effectively suppresses tumor cell growth by inducing apoptosis, senescence, and autophagy, and causes sensitization to chemoradiation therapies in a cellular context-dependent manner. Signal molecules that determine the cell fate upon MLN4924 treatment, however, remain elusive. Cancer cells develop MLN4924 resistance by selecting target mutations. FUTURE DIRECTIONS: In the clinical side, several Phase 1b trials are under way to determine the safety and efficacy of MLN4924, acting alone or in combination with conventional chemotherapy, against human solid tumors. In the preclinical side, the efforts are being made to develop additional neddylation inhibitors by targeting NEDD8 E2s and E3s.
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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.