ArticleProceedings of the National Academy of Sciences of the United States of America2015
Inactivation of EWS reduces PGC-1α protein stability and mitochondrial homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Mitochondrial Quality Control in Age-Related Diseases: From Molecular Architecture to Precision Therapeutics.Antioxidants (Basel, Switzerland) · 2026Review
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Article
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- Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- In-depth proteome analysis of brain tissue from Ewsr1 knockout mouse by multiplexed isobaric tandem mass tag labeling.Scientific reports · 2023Article
- EWSR1 prevents the induction of aneuploidy through direct regulation of Aurora B.Frontiers in cell and developmental biology · 2023Article
- FBXW7 alleviates hyperglycemia-induced endothelial oxidative stress injury via ROS and PARP inhibition.Redox biology · 2022Article
- Podocyte Injury in Diabetic Kidney Disease: A Focus on Mitochondrial Dysfunction.Frontiers in cell and developmental biology · 2022Review
- Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential.International journal of molecular sciences · 2021Review
- The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS.Antioxidants (Basel, Switzerland) · 2021Review
- Mitophagy receptor FUNDC1 is regulated by PGC-1α/NRF1 to fine tune mitochondrial homeostasis.EMBO reports · 2021Article
- Rationale for Early Detection ofCancers · 2021Review
- Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from chromatin.EMBO reports · 2020Article
- Silk Fibroin Promotes the Regeneration of Pancreatic β-Cells in the C57BL/KsJ-Molecules (Basel, Switzerland) · 2020Article
- Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases.Cell stress · 2020Review
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein that is frequently rearranged in a number of different cancers by chromosomal translocations. Physiologically, EWS has diverse and essential roles in various organ development and cellular processes. In this study, we uncovered a new role of EWS in mitochondrial homeostasis and energy metabolism. Loss of EWS leads to a significant decrease in mitochondria abundance and activity, which is caused by a rapid degradation of Peroxisome proliferator-activated receptor γ Coactivator (PGC-1α), a central regulator of mitochondria biogenesis, function, and cellular energy metabolism. EWS inactivation leads to increased ubiquitination and proteolysis of PGC-1α via proteasome pathway. Complementation of EWS in Ews-deficient cells restores PGC-1α and mitochondrial abundance. We found that expression of E3 ubiquitin ligase, FBXW7 (F-box/WD40 domain protein 7), is increased in the absence of Ews and depletion of Fbxw7 in Ews-null cells restores PGC-1α expression and mitochondrial density. Consistent with these findings, mitochondrial abundance and activity are significantly reduced in brown fat and skeletal muscles of Ews-deficient mice. Furthermore, expression of mitochondrial biogenesis, respiration and fatty acid β-oxidation genes is significantly reduced in the liver of Ews-null mice. These results demonstrate a novel role of EWS in mitochondrial and cellular energy homeostasis by controlling PGC-1α protein stability, and further implicate altered mitochondrial and energy metabolism in cancers harboring the EWS translocation.
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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.