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Updated: Jun 26, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

O-GlcNAcylation is involved in the transcriptional activity of EWS-FLI1 in Ewing's sarcoma

R Bachmaier1, D N T Aryee, G Jug

  • 1Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.

Oncogene
|January 20, 2009
PubMed

Insights

Ewing

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ewing's sarcoma family tumors (ESFTs) are driven by the oncogenic transcription factor EWS-FLI1.
  • Targeting EWS-FLI1 activity is a promising therapeutic strategy for ESFTs.
  • Post-translational modifications regulate transcription factor activity.

Purpose of the Study:

  • To investigate post-translational modifications of the EWS-FLI1 oncoprotein.
  • To explore the functional impact of these modifications on EWS-FLI1 activity and ESFT pathogenesis.

Main Methods:

  • Immuno-purification of EWS-FLI1 fusion protein.
  • Antibody detection for O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation).
  • Phosphoprotein staining, phosphatase inhibition, and mutation analysis.
  • Metabolic inhibition of the hexosamine biosynthetic pathway.

Main Results:

  • EWS-FLI1 is modified by O-GlcNAcylation and phosphorylation, with dynamic interplay between these modifications.
  • O-GlcNAcylation occurs at Ser/Thr residues within the EWS N-terminal transcriptional-activation domain.
  • Inhibition of O-GlcNAcylation via hexosamine pathway blockade specifically impaired EWS-FLI1's transcriptional activation of the Id2 gene.
  • Phosphatase inhibition increased EWS-FLI1 molecular weight and decreased O-GlcNAc levels.

Conclusions:

  • EWS-FLI1 undergoes dynamic O-GlcNAcylation and phosphorylation.
  • Modulating EWS-FLI1 glycosylation interferes with its oncogenic transcriptional activity.
  • Targeting EWS-FLI1 glycosylation pathways represents a potential novel therapeutic approach for ESFTs.

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