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KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) is very aggressive and lacks specific therapeutic targets. Ribosome RNAs (rRNAs) are central components of ribosomes and transcribed in nucleoli, and the level of rRNA transcription greatly affects ribosome production and cell proliferation. We have reported that...

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Autores principales: Okamoto, Kengo, Tanaka, Yuji, Ogasawara, Sachiko, Obuse, Chikashi, Nakayama, Jun-ichi, Yano, Hirohisa, Tsuneoka, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677663/
https://www.ncbi.nlm.nih.gov/pubmed/31413816
http://dx.doi.org/10.18632/oncotarget.27092
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author Okamoto, Kengo
Tanaka, Yuji
Ogasawara, Sachiko
Obuse, Chikashi
Nakayama, Jun-ichi
Yano, Hirohisa
Tsuneoka, Makoto
author_facet Okamoto, Kengo
Tanaka, Yuji
Ogasawara, Sachiko
Obuse, Chikashi
Nakayama, Jun-ichi
Yano, Hirohisa
Tsuneoka, Makoto
author_sort Okamoto, Kengo
collection PubMed
description Triple-negative breast cancer (TNBC) is very aggressive and lacks specific therapeutic targets. Ribosome RNAs (rRNAs) are central components of ribosomes and transcribed in nucleoli, and the level of rRNA transcription greatly affects ribosome production and cell proliferation. We have reported that an epigenetic protein, KDM2A, exists in nucleoli and reduces rRNA transcription on glucose starvation. However, the molecular mechanism is still unclear. The purpose of this study is to examine the KDM2A-dependent regulation mechanism of rRNA transcription. In this study, we turned our attention to the nucleolar accumulation of KDM2A. We found that KDM2A had multiple regions for its nucleolar localization, and one of the regions was directly bound by heterochromatin protein 1γ (HP1γ) using valine 801 in the LxVxL motif of KDM2A. A knockdown of HP1γ or a point mutation of valine 801 in KDM2A decreased the nucleolar accumulation of KDM2A, and suppressed the reduction of rRNA transcription on glucose starvation. These results uncovered a novel function of HP1γ: the regulation of rRNA transcription, and suggested that HP1γ stimulates the nucleolar accumulation of KDM2A to support the KDM2A-dependent regulation of rRNA transcription. HP1γ was expressed in cancer cells in all breast carcinoma tissues examined, including TNBC tissues. A knockdown of HP1γ in a TNBC cell line, MDA-MB-231 cells, reduced the nucleolar accumulation of KDM2A, and suppressed the reductions of rRNA transcription and cell proliferation on glucose starvation. These results suggest that the KDM2A-dependent regulation of rRNA transcription requires HP1γ, and thus may be applicable to the treatment of TNBC.
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spelling pubmed-66776632019-08-14 KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells Okamoto, Kengo Tanaka, Yuji Ogasawara, Sachiko Obuse, Chikashi Nakayama, Jun-ichi Yano, Hirohisa Tsuneoka, Makoto Oncotarget Research Paper Triple-negative breast cancer (TNBC) is very aggressive and lacks specific therapeutic targets. Ribosome RNAs (rRNAs) are central components of ribosomes and transcribed in nucleoli, and the level of rRNA transcription greatly affects ribosome production and cell proliferation. We have reported that an epigenetic protein, KDM2A, exists in nucleoli and reduces rRNA transcription on glucose starvation. However, the molecular mechanism is still unclear. The purpose of this study is to examine the KDM2A-dependent regulation mechanism of rRNA transcription. In this study, we turned our attention to the nucleolar accumulation of KDM2A. We found that KDM2A had multiple regions for its nucleolar localization, and one of the regions was directly bound by heterochromatin protein 1γ (HP1γ) using valine 801 in the LxVxL motif of KDM2A. A knockdown of HP1γ or a point mutation of valine 801 in KDM2A decreased the nucleolar accumulation of KDM2A, and suppressed the reduction of rRNA transcription on glucose starvation. These results uncovered a novel function of HP1γ: the regulation of rRNA transcription, and suggested that HP1γ stimulates the nucleolar accumulation of KDM2A to support the KDM2A-dependent regulation of rRNA transcription. HP1γ was expressed in cancer cells in all breast carcinoma tissues examined, including TNBC tissues. A knockdown of HP1γ in a TNBC cell line, MDA-MB-231 cells, reduced the nucleolar accumulation of KDM2A, and suppressed the reductions of rRNA transcription and cell proliferation on glucose starvation. These results suggest that the KDM2A-dependent regulation of rRNA transcription requires HP1γ, and thus may be applicable to the treatment of TNBC. Impact Journals LLC 2019-07-30 /pmc/articles/PMC6677663/ /pubmed/31413816 http://dx.doi.org/10.18632/oncotarget.27092 Text en Copyright: © 2019 Okamoto et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Okamoto, Kengo
Tanaka, Yuji
Ogasawara, Sachiko
Obuse, Chikashi
Nakayama, Jun-ichi
Yano, Hirohisa
Tsuneoka, Makoto
KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells
title KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells
title_full KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells
title_fullStr KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells
title_full_unstemmed KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells
title_short KDM2A-dependent reduction of rRNA transcription on glucose starvation requires HP1 in cells, including triple-negative breast cancer cells
title_sort kdm2a-dependent reduction of rrna transcription on glucose starvation requires hp1 in cells, including triple-negative breast cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677663/
https://www.ncbi.nlm.nih.gov/pubmed/31413816
http://dx.doi.org/10.18632/oncotarget.27092
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