ArticleBMC cancer2012
Junction region of EWS-FLI1 fusion protein has a dominant negative effect in Ewing's sarcoma in vitro.
Article in BMC cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Druggable upregulated proteins in EWS-FLI-driven Ewing sarcoma as emerging new therapeutic targets.American journal of translational research · 2025Review
- Regulation of EWSR1-FLI1 Function by Post-Transcriptional and Post-Translational Modifications.Cancers · 2023Review
- Emerging Pharmacotherapeutic Strategies to Overcome Undruggable Proteins in Cancer.International journal of biological sciences · 2023Review
- TheBiomolecular NMR assignments · 2022Article
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
- Challenges in modeling EWS-FLI1-driven transgenic mouse model for Ewing sarcoma.American journal of translational research · 2021Review
- An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis.PloS one · 2020Article
- A polypeptide from the junction region sequence of EWS-FLI1 inhibits Ewing's sarcoma cells, interacts with the EWS-FLI1 and partner proteins.Scientific reports · 2017Article
- Indian data on bone and soft tissue sarcomas: A summary of published study results.South Asian journal of cancerReview
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEwing's sarcoma is a malignancy characterized by a specific 11:22 chromosomal translocation which generates a novel EWS-FLI1 fusion protein functioning as an aberrant transcription factor. In the present study, we have further characterized the junction region of the EWS-FLI1 fusion protein.
methodsIn-silico model of EWS-FLI1 fusion protein was analysed for ligand binding sites, and a putative region (amino acid (aa) 251-343 of the type 1 fusion protein) in the vicinity of the fusion junction was cloned and expressed using bacterial expression. The recombinant protein was characterized by Circular Dichroism (CD). We then expressed aa 251-280 ectopically in Ewing's sarcoma cell-line and its effect on cell proliferation, tumorigenicity and expression of EWS-FLI1 target genes were analysed.
resultsOur modelling analysis indicated that Junction region (aa 251-343) encompasses potential ligand biding sites in the EWS-FLI1 protein and when expressed in bacteria was present as soluble form. Ectopically expressing this region in Ewing's sarcoma cells inhibited tumorigenicity, and EWS-FLI1 target genes indicating a dominant negative biological effect.
conclusionsJunction region can be exploited further as target for drug development in future to specifically target EWS-FLI1 in Ewing's Sarcoma.
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