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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531837/?tool=EBI
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author 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
author_facet 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
author_sort Takao Kitagawa
collection DOAJ
description 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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spelling doaj.art-b3e216d645cb41128dbf5f0f447ef6f22022-12-22T04:29:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011710AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cellsTakao KitagawaDaiki KobayashiByron BaronHajime OkitaTatsuo MiyamotoRie TakaiDurga PaudelTohru OhtaYoichi AsaokaMasayuki TokunagaKoji NakagawaMakoto Furutani-SeikiNorie ArakiYasuhiro KuramitsuMasanobu KobayashiEwing’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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531837/?tool=EBI
spellingShingle 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
AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cells
PLoS ONE
title AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cells
title_full AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cells
title_fullStr AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cells
title_full_unstemmed AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cells
title_short AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cells
title_sort at hook dna binding motif containing protein one knockdown downregulates ews fli1 transcriptional activity in ewing s sarcoma cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531837/?tool=EBI
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