# Ewing sarcoma: fusion protein structure/function relationships that reprogram transcription

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2020 · $201,045

## Abstract

Abstract:
 Ewing sarcoma is the second most common pediatric bone cancer. These tumors are
particularly malignant, as 25% of patients will be metastatic at the time of diagnosis. The five-
year survival rate for patients with primary Ewing sarcoma is 64% and less than 30% for patients
with disseminated disease. Nearly all of Ewing sarcomas are caused by a translocation between
either EWS or FUS and FLI1, creating a powerful tumor-causing fusion protein, EWS-FLI1 or
FUS-FLI1. FUS, EWS, and TAF15 are transcription factors that together form the FET family of
proteins. We will explore interactions between FET proteins and fusion proteins in Ewing
sarcoma that regulate transcription and thereby promote tumor formation. We propose that large
transcription granules formed by FET proteins serve to localize transcription machineries to
active sites of gene expression. We hypothesize that fusion proteins formed from FUS or EWS
drive transcription granules to constitutively form at poly-GGAA sites in the genome.
 Launching our investigation into the basic molecular mechanisms by which FET fusion
proteins contribute and drive pediatric sarcoma initiation, progression, and metastasis, we
propose two aims. The goal of these aims is to (1) test a model that fusion proteins work hand-in-
glove with the wildtype variants to reprogram cells toward disease and (2) establish the basic
biochemical frameworks for FET-fusion structure/function relationships in our in vitro transcription
assays. The result of these studies will well position us to identify and investigate key interactors
that modify FET and FET fusion protein activity in the disease-cellular environment.

## Key facts

- **NIH application ID:** 9850221
- **Project number:** 5R21CA238499-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Jacob C. Schwartz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,045
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850221

## Citation

> US National Institutes of Health, RePORTER application 9850221, Ewing sarcoma: fusion protein structure/function relationships that reprogram transcription (5R21CA238499-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850221. Licensed CC0.

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