AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewings sarcoma cells

Kitagawa, T.; Kobayashi, D.; Baron, B.; Okita, H.; Miyamoto, T.; Takai, R.; Paudel, D.; Ohta, T.; Asaoka, Y.; Tokunaga, M.; Furutani-Seiki, M.; Araki, N.; Kuramitsu, Y.; Kobayashi, M.

doi:10.1101/2022.05.16.492174

bioRxiv · 10.1101/2022.05.16.492174

AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewings sarcoma cells

Kitagawa, T.·Kobayashi, D.·Baron, B.·Okita, H.·Miyamoto, T.·Takai, R.·Paudel, D.·Ohta, T.·Asaoka, Y.·Tokunaga, M.·Furutani-Seiki, M.·Araki, N.·Kuramitsu, Y.·Kobayashi, M.

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Abstract

Ewings 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 Ewings 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. In addition, AHDC1 co-localized with BRD4. Our results suggest that AHDC1 supports cell growth through EWS-FLI1.

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Kitagawa, T., Kobayashi, D., Baron, B., Okita, H., Miyamoto, T., Takai, R., Paudel, D., Ohta, T., Asaoka, Y., Tokunaga, M., Furutani-Seiki, M., Araki, N., Kuramitsu, Y., Kobayashi, M.. 2022-05-16. AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewings sarcoma cells. https://doi.org/10.1101/2022.05.16.492174

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