ArticleMolecular & cellular proteomics : MCP2015
The neddylation-cullin 2-RBX1 E3 ligase axis targets tumor suppressor RhoB for degradation in liver cancer.
Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- The impact of neddylation on prognosis in the immune microenvironment of neuroblastoma: a single-cell transcriptomic analysis.Immunologic research · 2025Article
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- Mevalonate pathway inhibition reduces bladder cancer metastasis by modulating RhoB protein stability and integrin β1 localization.Communications biology · 2024Article
- Neddylation signaling inactivation by tetracaine hydrochloride suppresses cell proliferation and alleviates vemurafenib-resistance of melanoma.Cell biology and toxicology · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- Pevonedistat Suppresses Pancreatic Cancer GrowthFrontiers in oncology · 2022Article
- Genetic and Epigenetic Mechanisms Deregulate the CRL2Frontiers in genetics · 2022Article
- A polydopamine nanomedicine used in photothermal therapy for liver cancer knocks down the anti-cancer target NEDD8-E3 ligase ROC1 (RBX1).Journal of nanobiotechnology · 2021Article
- Cullin 2-RBX1 E3 ligase and USP2 regulate antithrombin ubiquitination and stability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Prognostic value of ubiquitin E2 UBE2W and its correlation with tumor-infiltrating immune cells in breast cancer.BMC cancer · 2021Article
- [Research progress of neural precursor cells-expressed developmentally down-regulated protein-8 in liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Article
- Ubiquitination-Dependent Regulation of Small GTPases in Membrane Trafficking: From Cell Biology to Human Diseases.Frontiers in cell and developmental biology · 2021Review
- Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies.Journal of hematology & oncology · 2020Review
- Neddylation inhibition activates the protective autophagy through NF-κB-catalase-ATF3 Axis in human esophageal cancer cells.Cell communication and signaling : CCS · 2020Article
- The RNA polymerase III repressor MAF1 is regulated by ubiquitin-dependent proteasome degradation and modulates cancer drug resistance and apoptosis.The Journal of biological chemistry · 2019Article
- Article
- An overactive neddylation pathway serves as a therapeutic target and MLN4924 enhances the anticancer activity of cisplatin in pancreatic cancer.Oncology letters · 2019Article
- The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma.Cell proliferation · 2019Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neddylation-cullin-RING E3 ligase (CRL) pathway has recently been identified as a potential oncogenic event and attractive anticancer target; however, its underlying mechanisms have not been well elucidated. In this study, RhoB, a well known tumor suppressor, was identified and validated with an iTRAQ-based quantitative proteomic approach as a new target of this pathway in liver cancer cells. Specifically, cullin 2-RBX1 E3 ligase, which requires NEDD8 conjugation for its activation, interacted with RhoB and promoted its ubiquitination and degradation. In human liver cancer tissues, the neddylation-CRL pathway was overactivated and reversely correlated with RhoB levels. Moreover, RhoB accumulation upon inhibition of the neddylation-CRL pathway for anticancer therapy contributed to the induction of tumor suppressors p21 and p27, apoptosis, and growth suppression. Our findings highlight the degradation of RhoB via the neddylation-CRL pathway as an important molecular event that drives liver carcinogenesis and RhoB itself as a pivotal effector for anticancer therapy targeting this oncogenic pathway.
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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.