ArticleCell death and differentiation2016
The ubiquitin ligase Smurf2 suppresses TGFβ-induced epithelial-mesenchymal transition in a sumoylation-regulated manner.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- The role of ubiquitin system in ageing-related diseases and potential therapeutic opportunities.Molecular biomedicine · 2026Review
- Importance of SUMOylation Consensus Sequence of MAFK in Regulating EMT, Tumor Growth, Stemness, and Drug Resistance.Cancer science · 2026Article
- The role of SUMOylation in epithelial-mesenchymal transition.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Association of mitochondrial phosphoenolpyruvate carboxykinase with prognosis and immune regulation in hepatocellular carcinoma.Scientific reports · 2024Article
- The regulatory roles of Smad2/3 protein andInternational journal of reproductive biomedicine · 2024Article
- Article
- YTHDF2 governs muscle size through a targeted modulation of proteostasis.Nature communications · 2024Article
- Cbfβ regulates Wnt/β-catenin, Hippo/Yap, and TGFβ signaling pathways in articular cartilage homeostasis and protects from ACLT surgery-induced osteoarthritis.bioRxiv : the preprint server for biology · 2024Article
- Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.Theranostics · 2024Review
- Deficiency of Cbfβ in articular cartilage leads to osteoarthritis-like phenotype through Hippo/Yap, TGFβ, and Wnt/β-catenin signaling pathways.International journal of biological sciences · 2024Article
- Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.Frontiers in oncology · 2024Review
- The SUMOylation and ubiquitination crosstalk in cancer.Journal of cancer research and clinical oncology · 2023Review
- Unraveling the Molecular Puzzle: Exploring Gene Networks across Diverse EMT Status of Cell Lines.International journal of molecular sciences · 2023Review
- Sumoylated SnoN interacts with HDAC1 and p300/CBP to regulate EMT-associated phenotypes in mammary organoids.Cell death & disease · 2023Article
- The role of NEDD4 related HECT-type E3 ubiquitin ligases in defective autophagy in cancer cells: molecular mechanisms and therapeutic perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
- Runx1 is a key regulator of articular cartilage homeostasis by orchestrating YAP, TGFβ, and Wnt signaling in articular cartilage formation and osteoarthritis.Bone research · 2022Article
- TRAF4 hyperactivates HER2 signaling and contributes to Trastuzumab resistance in HER2-positive breast cancer.Oncogene · 2022Article
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- Tumor-suppressive role of Smad ubiquitination regulatory factor 2 in patients with colorectal cancer.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) is a fundamental cellular process in epithelial tissue development, and can be reactivated in cancer contributing to tumor invasiveness and metastasis. The cytokine transforming growth factor-β (TGFβ) is a key inducer of EMT, but the mechanisms that regulate TGFβ-induced EMT remain incompletely understood. Here, we report that knockdown of the ubiquitin ligase Smurf2 promotes the ability of TGFβ to induce EMT in a three-dimensional cell culture model of NMuMG mammary epithelial cells. In other studies, we identify Smurf2 as a target of the small ubiquitin like modifier (SUMO) pathway. We find that the SUMO-E2 conjugating enzyme Ubc9 and the SUMO E3 ligase PIAS3 associate with Smurf2 and promote its sumoylation at the distinct sites of Lysines 26 and 369. The sumoylation of Smurf2 enhances its ability to induce the degradation of the TGFβ receptor and thereby suppresses EMT in NMuMG cells. Collectively, our data reveal that Smurf2 acts in a sumoylation-regulated manner to suppress TGFβ-induced EMT. These findings have significant implications for our understanding of epithelial tissue development and cancer.
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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.