ArticleScientific reports2017
MLN4924 (Pevonedistat), a protein neddylation inhibitor, suppresses proliferation and migration of human clear cell renal cell carcinoma.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 72 citations in OpenAlex.
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Unbiased CRISPR synthetic lethal screening for genetic vulnerabilities in a succinate dehydrogenase-loss model of paraganglioma.iScience · 2026Article
- NEDDylation maintains oocyte quality by stabilizing mitochondrial transcription.Science advances · 2026Article
- Multi-omics analysis of patient-derived organoids reveals that E3 ligase COP1 promotes liver metastasis and oxaliplatin resistance in colorectal cancer through LUZP1 degradation and MYL9 phosphorylation.Experimental hematology & oncology · 2026Article
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Utilization of Functional Degradation Pathways for the Characterization of Ubiquitin-Proteasome System Tool Compounds.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The role of neddylation in colorectal cancer and its therapeutic potential.Discover oncology · 2025Review
- Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules.ACS central science · 2025Article
- PRMT1-mediated methylation of UBE2m promoting calcium oxalate crystal-induced kidney injury by inhibiting fatty acid metabolism.Cell death & disease · 2025Article
- MicroRNA-1303 in cancer pathogenesis and therapy: clinical implications for biomarker development and targeted treatment strategies.Cancer cell international · 2025Review
- Nanomedicine Approaches for Autophagy Modulation in Cancer Therapy.Small science · 2025Article
- HDAC3 genetic and pharmacologic inhibition radiosensitizes fusion positive rhabdomyosarcoma by promoting DNA double-strand breaks.Cell death discovery · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Review
- 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
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Article
- Ubiquitination of NKCC2 by the cullin-RING E3 ubiquitin ligase family in the thick ascending limb of the loop of Henle.American journal of physiology. Renal physiology · 2023Article
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6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers cell-cycle arrest, apoptosis, senescence and autophagy in many cancer cells. In this study, we investigated the anti-tumor effect of MLN4924 in human clear cell renal carcinoma (ccRCC). Levels of both Nedd8 activating enzyme E1 and Nedd8-conjugating enzyme E2 were higher in ccRCC tissues and RCC cancer cells than in normal. Moreover, MLN4924 treatment led to rapid inhibition of Cullin1 neddylation and notably suppressed growth and survival as well as migration in a dose-and time-dependent manner. Mechanistic studies revealed that MLN4924 induced the accumulation of a number of CRL substrates, including p21, p27 and Wee1 to trigger DNA damage and induce growth arrest at the G2/M phase. MLN4924 also induced anti-migration and anti-invasion by activating E-cadherin and repressing Vimentin. Taken together, this study provides the first evidence that neddylation pathway is overactive in ccRCC and that MLN4924 induces dose-dependent anti-proliferation, anti-migration, anti-invasion in ccRCC cells. The study thus indicates that MLN4924 has potential therapeutic value for the clinical treatment of renal cancer.
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