Journal
PLOS ONE
Volume 17, Issue 10, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0269077
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Funding
- Japan Society for the Promotion of Science [18K07199]
- Takeda Science Foundation [2019081196]
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It has been discovered that AHDC1 is a proximal protein of EWS-ETS fusion proteins and supports cell growth through interaction with EWS-FLI1. Knockdown of AHDC1 reduces cell growth and transcriptional activity of EWS-FLI1, as well as the levels of interacting proteins BRD4 and BRG1.
Ewing's sarcoma is the second most common bone malignancy in children or young adults and is caused by an oncogenic transcription factor by a chromosomal translocation between the EWSR1 gene and the ETS transcription factor family. However, the transcriptional mechanism of EWS-ETS fusion proteins is still unclear. To identify the transcriptional complexes of EWS-ETS fusion transcription factors, we applied a proximal labeling system called BioID in Ewing's sarcoma cells. We identified AHDC1 as a proximal protein of EWS-ETS fusion proteins. AHDC1 knockdown showed a reduced cell growth and transcriptional activity of EWS-FLI1. AHDC1 knockdown also reduced BRD4 and BRG1 protein levels, both known as interacting proteins of EWS-FLI1. Our results suggest that AHDC1 supports cell growth through EWS-FLI1.
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