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Updated: Oct 25, 2025
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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
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The oncogenic transcription factor FUS-CHOP can undergo nuclear liquid-liquid phase separation
Izzy Owen1, Debra Yee1, Hala Wyne1
1Department of Biochemistry and Molecular Biology, Uniformed Services University, Bethesda, MD 20814, USA.
Journal of Cell Science
|August 6, 2021
Summary
Myxoid liposarcoma involves the FUS-CHOP fusion protein, which drives cancer by forming unique cellular condensates. Targeting these FUS-CHOP phase transitions offers a potential new therapeutic strategy for this sarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Myxoid liposarcoma arises from a FUS-CHOP fusion protein.
- FUS regulates RNA metabolism, while CHOP is a stress-induced transcription factor.
- The oncogenic mechanism of FUS-CHOP, particularly transcriptional activation, remains unclear.
Purpose of the Study:
- To investigate the phase-separating properties of the FUS-CHOP fusion protein.
- To elucidate the role of these properties in oncogenic transformation and transcriptional activation.
- To explore FUS-CHOP phase transitions as a potential therapeutic target for myxoid liposarcoma.
Main Methods:
- Characterization of FUS-CHOP in cellular and in vitro models.
- Assessment of phase separation properties compared to unmodified CHOP.
- Colocalization studies with BRD4, a marker for super enhancer condensates.
Main Results:
- FUS-CHOP exhibits novel phase-separating properties distinct from CHOP.
- FUS-CHOP forms phase-separated condensates within cells.
- These condensates colocalize with BRD4, suggesting a link to super enhancers.
Conclusions:
- The N-terminus of FUS drives nuclear phase transitions in FUS-CHOP.
- FUS-CHOP-induced phase separation represents a novel oncogenic mechanism.
- Targeting FUS-CHOP phase transitions presents a promising therapeutic avenue for myxoid liposarcoma.
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