ArticleNucleic acids research2014
Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 101 citations in OpenAlex.
- FBXO28 targets SNAI1 for ubiquitin-proteasomal degradation in non-small cell lung cancer.The Journal of biological chemistry · 2026Article
- FBXL5 depletion as a novel strategy against osteosarcoma: Evidence for MEK/ERK inhibition and enhanced therapeutic sensitivity.Oncology letters · 2026Article
- DTX3L Inhibits the EMT, Metastasis, and Stem-Like Features of Gastric Cancer Through Promoting GSK-3β Dependent SNAI1 Decay.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulatory mechanisms for Snail protein stability: ubiquitin-proteasome system and chaperone-mediated autophagy.Experimental & molecular medicine · 2026Review
- UBR5 regulates the progression of colorectal cancer cells through Snail-induced epithelial-mesenchymal transition.Genes & diseases · 2026Article
- Targeting FBXL5 to induce ferroptosis and reverse oxaliplatin resistance in iron-rich colorectal cancer.Scientific reports · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Control of Snail1 protein stability by post-translational modifications: the basis for a complex regulation of Snail1 function.International journal of biological sciences · 2025Review
- Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis.Molecular cancer · 2024Article
- FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells.Cancers · 2024Article
- Article
- Dissecting the multifaceted roles of autophagy in cancer initiation, growth, and metastasis: from molecular mechanisms to therapeutic applications.Medical oncology (Northwood, London, England) · 2024Review
- FBXL8 inhibits post-myocardial infarction cardiac fibrosis by targeting Snail1 for ubiquitin-proteasome degradation.Cell death & disease · 2024Article
- MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases.Cancer research communications · 2024Article
- UCHL1 contributes to insensitivity to endocrine therapy in triple-negative breast cancer by deubiquitinating and stabilizing KLF5.Breast cancer research : BCR · 2024Article
- Ubiquitin-specific Protease 35 Promotes Gastric Cancer Metastasis by Increasing the Stability of Snail1.International journal of biological sciences · 2024Article
- ERK3 Increases Snail Protein Stability by Inhibiting FBXO11-Mediated Snail Ubiquitination.Cancers · 2023Article
- Distinct functions between ferrous and ferric iron in lung cancer cell growth.Cancer science · 2023Article
- USP2 promotes cell proliferation and metastasis in choroidal melanoma via stabilizing Snail.Journal of cancer research and clinical oncology · 2023Article
- Noncanonical Wnt signaling promotes colon tumor growth, chemoresistance and tumor fibroblast activation.EMBO reports · 2023Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The zinc finger transcription factor Snail1 regulates epithelial to mesenchymal transition, repressing epithelial markers and activating mesenchymal genes. Snail1 is an extremely labile protein degraded by the cytoplasmic ubiquitin-ligases β-TrCP1/FBXW1 and Ppa/FBXL14. Using a short hairpin RNA screening, we have identified FBXL5 as a novel Snail1 ubiquitin ligase. FBXL5 is located in the nucleus where it interacts with Snail1 promoting its polyubiquitination and affecting Snail1 protein stability and function by impairing DNA binding. Snail1 downregulation by FBXL5 is prevented by Lats2, a protein kinase that phosphorylates Snail1 precluding its nuclear export but not its polyubiquitination. Actually, although polyubiquitination by FBXL5 takes place in the nucleus, Snail1 is degraded in the cytosol. Finally, FBXL5 is highly sensitive to stress conditions and is downregulated by iron depletion and γ-irradiation, explaining Snail1 stabilization in these conditions. These results characterize a novel nuclear ubiquitin ligase controlling Snail1 protein stability and provide the molecular basis for understanding how radiotherapy upregulates the epithelial to mesenchymal transition-inducer Snail1.
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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.