ArticleScientific reports2019
USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Modelling EWS::FLI1 protein fluctuations reveal determinants of tumor plasticity in Ewing sarcoma.EMBO molecular medicine · 2026Article
- Suppressing the Aberrant Transcriptional Functionality of EWS::FLI1 Oncoprotein by Designer polyQ Fusions with Its Homologous Peptides.Biomedicines · 2026Article
- Deubiquitinase USP6 stabilizes oncogenic RUNX1 fusion proteins to promote the leukemic potential and malignant progression.Leukemia · 2025Article
- The O-glycosyltransferase C1GALT1 promotes EWSR1::FLI1 expression and is a therapeutic target for Ewing sarcoma.Nature communications · 2025Article
- PROTAC-Based Protein Degradation as a Promising Strategy for Targeted Therapy in Sarcomas.International journal of molecular sciences · 2023Review
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- Regulation of EWSR1-FLI1 Function by Post-Transcriptional and Post-Translational Modifications.Cancers · 2023Review
- The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review.Frontiers in oncology · 2022Review
- Emerging Role of Ubiquitin-Specific Protease 19 in Oncogenesis and Cancer Development.Frontiers in cell and developmental biology · 2022Review
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
- SPOP and OTUD7A Control EWS-FLI1 Protein Stability to Govern Ewing Sarcoma Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect.International journal of molecular sciences · 2021Review
- Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development.International journal of molecular sciences · 2021Review
- USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer.Oncogenesis · 2021Article
- Ubiquitin specific peptidase 19 is a prognostic biomarker and affect the proliferation and migration of clear cell renal cell carcinoma.Oncology reports · 2020Article
- An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis.PloS one · 2020Article
- Development and validation of a novel immune-related prognostic model in lung squamous cell carcinoma.International journal of medical sciences · 2020Article
- Targeting the undruggable: exploiting neomorphic features of fusion oncoproteins in childhood sarcomas for innovative therapies.Cancer metastasis reviews · 2019Review
- RUNX2 Represses the EWS-FLI1-mediated Transcription in Ewing's Sarcoma Cells.Cancer genomics & proteomicsArticle
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ewing sarcoma is the second most common pediatric bone and soft tissue tumor presenting with an aggressive behavior and prevalence to metastasize. The diagnostic translocation t(22;11)(q24;12) leads to expression of the chimeric oncoprotein EWS-FLI1 which is uniquely expressed in all tumor cells and maintains their survival. Constant EWS-FLI1 protein turnover is regulated by the ubiquitin proteasome system. Here, we now identified ubiquitin specific protease 19 (USP19) as a regulator of EWS-FLI1 stability using an siRNA based screening approach. Depletion of USP19 resulted in diminished EWS-FLI1 protein levels and, vice versa, upregulation of active USP19 stabilized the fusion protein. Importantly, stabilization appears to be specific for the fusion protein as it could not be observed neither for EWSR1 nor for FLI1 wild type proteins even though USP19 binds to the N-terminal EWS region to regulate deubiquitination of both EWS-FLI1 and EWSR1. Further, stable shUSP19 depletion resulted in decreased cell growth and diminished colony forming capacity in vitro, and significantly delayed tumor growth in vivo. Our findings not only provide novel insights into the importance of the N-terminal EWSR1 domain for regulation of fusion protein stability, but also indicate that inhibition of deubiquitinating enzyme(s) might constitute a novel therapeutic strategy in treatment of Ewing sarcoma.
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