ArticleNature communications2023
Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
24 citing papers in PubMed, 27 citations in OpenAlex.
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Identifying Neddylation-modified features to assess prognosis and immune efficacy in hepatocellular carcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Pro-tumourigenic effects of DCAF13 on the progression of colorectal cancer.Oncology letters · 2026Article
- UBE2M as a bridge spanning neddylation and cell cycle regulation in colorectal adenocarcinoma.Experimental & molecular medicine · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Cellular strategies for repairing trapped protein-DNA complexes.Frontiers in pharmacology · 2026Review
- The role of neddylation in colorectal cancer and its therapeutic potential.Discover oncology · 2025Review
- Neddylation related gene signature for prognostic biomarkers in colorectal cancer with integrated bioinformatics and experimental analysis.Discover oncology · 2025Article
- SNORA74A Drives Self-Renewal of Liver Cancer Stem Cells and Hepatocarcinogenesis Through Activation of Notch3 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Phase 1 studies of the indenoisoquinolines LMP776 and LMP744 in patients with solid tumors and lymphomas.Cancer chemotherapy and pharmacology · 2025Article
- DCAF13 influences breast cancer chemotherapy resistance through metabolic reprogramming by regulating c-Myc expression.Medical oncology (Northwood, London, England) · 2025Article
- DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer.Nature communications · 2025Article
- Review
- miR-326 overexpression inhibits colorectal cancer cell growth and proteasome activity by targeting PNO1: unveiling a novel therapeutic intervention strategy.Scientific reports · 2024Article
- DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway.Cellular and molecular life sciences : CMLS · 2024Article
- A Modular Biosensor Design for Quantitative Measurement of Free Nedd8.ACS sensors · 2024Article
- The cullin Rtt101 promotes ubiquitin-dependent DNA-protein crosslink repair across the cell cycle.Nucleic acids research · 2024Article
- Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential.Molecules (Basel, Switzerland) · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review).International journal of oncology · 2024Review
Corrections and comments
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Authors and funding
25 authors at 2 institutions in 1 country.
Funding
Abstract
Colorectal cancers (CRCs) are prevalent worldwide, yet current treatments remain inadequate. Using chemical genetic screens, we identify that co-inhibition of topoisomerase I (TOP1) and NEDD8 is synergistically cytotoxic in human CRC cells. Combination of the TOP1 inhibitor irinotecan or its bioactive metabolite SN38 with the NEDD8-activating enzyme inhibitor pevonedistat exhibits synergy in CRC patient-derived organoids and xenografts. Mechanistically, we show that pevonedistat blocks the ubiquitin/proteasome-dependent repair of TOP1 DNA-protein crosslinks (TOP1-DPCs) induced by TOP1 inhibitors and that the CUL4-RBX1 complex (CRL4) is a prominent ubiquitin ligase acting on TOP1-DPCs for proteasomal degradation upon auto-NEDD8 modification during replication. We identify DCAF13, a DDB1 and Cullin Associated Factor, as the receptor of TOP1-DPCs for CRL4. Our study not only uncovers a replication-coupled ubiquitin-proteasome pathway for the repair of TOP1-DPCs but also provides molecular and translational rationale for combining TOP1 inhibitors and pevonedistat for CRC and other types of cancers.
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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.