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Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex

Bromodomain-containing protein 8 (BRD8) is a subunit of the NuA4/TIP60-histone acetyltransferase complex. Although BRD8 has been considered to act as a co-activator of the complex, its biological role remains to be elucidated. Here, we uncovered that BRD8 accumulates in colorectal cancer cells throu...

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Autores principales: Yamaguchi, Kiyoshi, Nakagawa, Saya, Saku, Akari, Isobe, Yumiko, Yamaguchi, Rui, Sheridan, Paul, Takane, Kiyoko, Ikenoue, Tsuneo, Zhu, Chi, Miura, Masashi, Okawara, Yuya, Nagatoishi, Satoru, Kozuka-Hata, Hiroko, Oyama, Masaaki, Aikou, Susumu, Ahiko, Yuka, Shida, Dai, Tsumoto, Kouhei, Miyano, Satoru, Imoto, Seiya, Furukawa, Yoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139981/
https://www.ncbi.nlm.nih.gov/pubmed/37123243
http://dx.doi.org/10.1016/j.isci.2023.106563
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author Yamaguchi, Kiyoshi
Nakagawa, Saya
Saku, Akari
Isobe, Yumiko
Yamaguchi, Rui
Sheridan, Paul
Takane, Kiyoko
Ikenoue, Tsuneo
Zhu, Chi
Miura, Masashi
Okawara, Yuya
Nagatoishi, Satoru
Kozuka-Hata, Hiroko
Oyama, Masaaki
Aikou, Susumu
Ahiko, Yuka
Shida, Dai
Tsumoto, Kouhei
Miyano, Satoru
Imoto, Seiya
Furukawa, Yoichi
author_facet Yamaguchi, Kiyoshi
Nakagawa, Saya
Saku, Akari
Isobe, Yumiko
Yamaguchi, Rui
Sheridan, Paul
Takane, Kiyoko
Ikenoue, Tsuneo
Zhu, Chi
Miura, Masashi
Okawara, Yuya
Nagatoishi, Satoru
Kozuka-Hata, Hiroko
Oyama, Masaaki
Aikou, Susumu
Ahiko, Yuka
Shida, Dai
Tsumoto, Kouhei
Miyano, Satoru
Imoto, Seiya
Furukawa, Yoichi
author_sort Yamaguchi, Kiyoshi
collection PubMed
description Bromodomain-containing protein 8 (BRD8) is a subunit of the NuA4/TIP60-histone acetyltransferase complex. Although BRD8 has been considered to act as a co-activator of the complex, its biological role remains to be elucidated. Here, we uncovered that BRD8 accumulates in colorectal cancer cells through the inhibition of ubiquitin-dependent protein degradation by the interaction with MRG domain binding protein. Transcriptome analysis coupled with genome-wide mapping of BRD8-binding sites disclosed that BRD8 transactivates a set of genes independently of TIP60, and that BRD8 regulates the expression of multiple subunits of the pre-replicative complex in concert with the activator protein-1. Depletion of BRD8 induced cell-cycle arrest at the G1 phase and suppressed cell proliferation. We have also shown that the bromodomain of BRD8 is indispensable for not only the interaction with histone H4 or transcriptional regulation but also its own protein stability. These findings highlight the importance of bromodomain as a therapeutic target.
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spelling pubmed-101399812023-04-29 Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex Yamaguchi, Kiyoshi Nakagawa, Saya Saku, Akari Isobe, Yumiko Yamaguchi, Rui Sheridan, Paul Takane, Kiyoko Ikenoue, Tsuneo Zhu, Chi Miura, Masashi Okawara, Yuya Nagatoishi, Satoru Kozuka-Hata, Hiroko Oyama, Masaaki Aikou, Susumu Ahiko, Yuka Shida, Dai Tsumoto, Kouhei Miyano, Satoru Imoto, Seiya Furukawa, Yoichi iScience Article Bromodomain-containing protein 8 (BRD8) is a subunit of the NuA4/TIP60-histone acetyltransferase complex. Although BRD8 has been considered to act as a co-activator of the complex, its biological role remains to be elucidated. Here, we uncovered that BRD8 accumulates in colorectal cancer cells through the inhibition of ubiquitin-dependent protein degradation by the interaction with MRG domain binding protein. Transcriptome analysis coupled with genome-wide mapping of BRD8-binding sites disclosed that BRD8 transactivates a set of genes independently of TIP60, and that BRD8 regulates the expression of multiple subunits of the pre-replicative complex in concert with the activator protein-1. Depletion of BRD8 induced cell-cycle arrest at the G1 phase and suppressed cell proliferation. We have also shown that the bromodomain of BRD8 is indispensable for not only the interaction with histone H4 or transcriptional regulation but also its own protein stability. These findings highlight the importance of bromodomain as a therapeutic target. Elsevier 2023-04-01 /pmc/articles/PMC10139981/ /pubmed/37123243 http://dx.doi.org/10.1016/j.isci.2023.106563 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yamaguchi, Kiyoshi
Nakagawa, Saya
Saku, Akari
Isobe, Yumiko
Yamaguchi, Rui
Sheridan, Paul
Takane, Kiyoko
Ikenoue, Tsuneo
Zhu, Chi
Miura, Masashi
Okawara, Yuya
Nagatoishi, Satoru
Kozuka-Hata, Hiroko
Oyama, Masaaki
Aikou, Susumu
Ahiko, Yuka
Shida, Dai
Tsumoto, Kouhei
Miyano, Satoru
Imoto, Seiya
Furukawa, Yoichi
Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex
title Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex
title_full Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex
title_fullStr Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex
title_full_unstemmed Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex
title_short Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex
title_sort bromodomain protein brd8 regulates cell cycle progression in colorectal cancer cells through a tip60-independent regulation of the pre-rc complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139981/
https://www.ncbi.nlm.nih.gov/pubmed/37123243
http://dx.doi.org/10.1016/j.isci.2023.106563
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