# Interplay between ubiquitination and epigenetic regulation of EGFR signaling in gliomagenesis

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $339,609

## Abstract

Project Summary
While the impact of protein ubiquitination has been extensively studied in regulating functional protein-
protein interaction, protein subcellular localization and protein stability, the interplay between the
ubiquitination and epigenetic machinery in orchestrating EGFR signaling in gliomagenesis has not
been drawn our attention until recently. This project targets the new aspects of the ubiquitin-pathway
in regulating histone H2A that in turn modulates EGFR signaling pathway in gliomagenesis.
 Monoubiquitination of histone H2A is one of the most abundant histone posttranslational
modifications in mammalian cells. H2A ubiquitination represents an important mechanism for many
regulatory transcriptional programs. Accumulating evidence supports a role of H2A ubiquitination in
glioblastoma. However, how H2A ubiquitination is regulated in glioblastoma is unknown.
 Studies outlined in this proposal will exam the functions and mechanisms of an EGFR induced
lncRNA, Lnc-EPAT, in H2A ubiquitination and tumorigenesis of glioblastoma. We will use a variety of
molecular and cell-based assays, and animal models, to determine 1) whether the aberrant EGFR
activation causes Lnc-EPAT overexpression in glioblastoma and the mechanisms underlying EGFR
signaling-induced Lnc-EPAT expression; 2) the role and mechanisms for Lnc-EPAT in sustaining H2A
ubiquitination and epigenetic regulation of EGFR pathway; 3) the functional significance and
mechanisms of EGFR- Lnc-EPAT-H2Aub in glioblastoma tumorigenesis. Finally, we will determine
the clinical significance of our findings using human tumor specimens.
 We predict that completion of these studies will contribute to a better understanding of the
molecular mechanisms for H2A ubiquitination and glioblastoma tumorigenesis. Furthermore,
accomplishing our goals is highly relevant to the development of novel therapeutic agents that inhibit
Lnc-EPAT for better combating glioblastoma. Thus, our studies may revolutionize our understanding
and treating glioblastoma.

## Key facts

- **NIH application ID:** 9990876
- **Project number:** 5R01NS101959-05
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Suyun Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,609
- **Award type:** 5
- **Project period:** 2019-01-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990876

## Citation

> US National Institutes of Health, RePORTER application 9990876, Interplay between ubiquitination and epigenetic regulation of EGFR signaling in gliomagenesis (5R01NS101959-05). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9990876. Licensed CC0.

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