ArticleMolecular cell2016
FBXW7 Facilitates Nonhomologous End-Joining via K63-Linked Polyubiquitylation of XRCC4.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 128 citations in OpenAlex.
- FBXL18 activating AKT/CCND1 signaling pathway mediates radioresistance in esophageal squamous cell carcinoma.BMB reports · 2026Article
- Protist oxygen-sensing and the role of prolyl hydroxylase-regulation of E3(SCF) ubiquitin ligases.Biochimica et biophysica acta. General subjects · 2026Review
- Finely-tuned regulator of DNA repair: FBXW7-185aa may modulate glioblastoma radiosensitization and the tumor immune microenvironment.Translational oncology · 2026Article
- ISGylation of γH2AX retains MDC1 and facilitates homologous recombination repair causing radioresistance in esophageal adenocarcinoma.The Journal of biological chemistry · 2026Article
- Therapy-associated mutagenesis at CTCF binding sites is shaped by chromatin context and DNA repair capacity.bioRxiv : the preprint server for biology · 2026Article
- FBXW7 Targets the SPT6-ΔNp63 Axis for Degradation to Inhibit Esophageal Tumorigenesis Induced by 4-Nitroquinoline N-Oxide.MedComm · 2026Article
- O-GlcNAcylation of XRCC4 controls its stability and confers resistance to DNA double-strand break damage in cancer cells.Cell death & disease · 2026Article
- Post-translational modification networks in tumor radiosensitivity: mechanistic insights and therapeutic opportunities.Journal of translational medicine · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- FBXO2 Alleviates Intervertebral Disc Degeneration via Dual Mechanisms: Activating PINK1-Parkin Mitophagy and Ubiquitinating LCN2 to Suppress Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- FBXO10 Drives Hepatocellular Carcinoma Proliferation via K63-Linked Ubiquitination and Stabilization of FRMPD1.Current issues in molecular biology · 2025Article
- Inactivation of GH3.5 by COP1-mediated K63-linked ubiquitination promotes seedling hypocotyl elongation.Nature communications · 2025Article
- The FBXW7-KMT2 axis in cancer-associated fibroblasts controls tumor growth via an epigenetic-paracrine mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.Journal of virology · 2024Article
- Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
FBXW7 is a haploinsufficient tumor suppressor with loss-of-function mutations occurring in human cancers. FBXW7 inactivation causes genomic instability, but the mechanism remains elusive. Here we show that FBXW7 facilitates nonhomologous end-joining (NHEJ) repair and that FBXW7 depletion causes radiosensitization. In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7. SCF(FBXW7) E3 ligase then promotes polyubiquitylation of XRCC4 at lysine 296 via lysine 63 linkage for enhanced association with the Ku70/80 complex to facilitate NHEJ repair. Consistent with these findings, a small-molecule inhibitor that abrogates XRCC4 polyubiquitylation reduces NHEJ repair. Our study demonstrates one mechanism by which FBXW7 contributes to genome integrity and implies that inactivated FBXW7 in human cancers could be a strategy for increasing the efficacy of radiotherapy.
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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.