PLoS ONE (Jan 2022)

AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing's sarcoma cells.

  • Takao Kitagawa,
  • Daiki Kobayashi,
  • Byron Baron,
  • Hajime Okita,
  • Tatsuo Miyamoto,
  • Rie Takai,
  • Durga Paudel,
  • Tohru Ohta,
  • Yoichi Asaoka,
  • Masayuki Tokunaga,
  • Koji Nakagawa,
  • Makoto Furutani-Seiki,
  • Norie Araki,
  • Yasuhiro Kuramitsu,
  • Masanobu Kobayashi

DOI
https://doi.org/10.1371/journal.pone.0269077
Journal volume & issue
Vol. 17, no. 10
p. e0269077

Abstract

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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.