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Updated: May 14, 2026
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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
In Silico Prediction of EZHIP Post-Translational Modification Sites and Small-Molecule High-Throughput Screening for
Jimin Moon1, Jiwon Hwang1, Chan Chung1,2
1Department of New Biology, DGIST, Daegu, Korea.
Brain Tumor Research and Treatment
|May 12, 2026
Summary
This study reveals that the oncoprotein EZHIP, crucial in pediatric brain tumors, is regulated by signaling pathways. AMPK activation reduces EZHIP, while PKC activation increases it, offering therapeutic targets.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Posterior fossa group A (PFA) ependymoma is a pediatric brain tumor driven by epigenetic changes.
- EZHIP is a key oncogenic factor in PFA ependymoma, inhibiting PRC2 and causing H3K27me3 loss.
- Metformin reduces EZHIP, but its regulation mechanisms are unknown.
Purpose of the Study:
- To define the regulatory mechanisms of EZHIP.
- To identify signaling pathways controlling EZHIP stability.
- To explore therapeutic targeting strategies for EZHIP-driven cancers.
Main Methods:
- Generated a stable HEK293T reporter cell line for EZHIP assessment.
- Performed in silico post-translational modification prediction to identify regulatory sites.
- Conducted high-throughput screening of pathway-targeting compounds and secondary validation.
Main Results:
- Identified serine phosphorylation sites on EZHIP and implicated AMPK, MAPK, PKC, AKT, and CK2 pathways.
- AMPK activation significantly suppressed EZHIP protein levels and restored H3K27me3.
- PKC activation increased EZHIP protein levels, while AMPK activation decreased it.
Conclusions:
- EZHIP is a dynamically regulated oncoprotein controlled by post-translational signaling.
- AMPK and PKC have opposing effects on EZHIP stability.
- These findings define actionable mechanisms for targeting EZHIP-driven cancers.
