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Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A
The nucleolus, whose primary function is ribosome biogenesis, plays an essential role in p53 activation. Ribosome biogenesis is inhibited in response to cellular stress and several nucleolar proteins translocate from the nucleolus to the nucleoplasm, where they activate p53. In this study, we analys...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456663/ https://www.ncbi.nlm.nih.gov/pubmed/26044764 http://dx.doi.org/10.1038/srep10854 |
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author | Kumazawa, Takuya Nishimura, Kazuho Katagiri, Naohiro Hashimoto, Sayaka Hayashi, Yuki Kimura, Keiji |
author_facet | Kumazawa, Takuya Nishimura, Kazuho Katagiri, Naohiro Hashimoto, Sayaka Hayashi, Yuki Kimura, Keiji |
author_sort | Kumazawa, Takuya |
collection | PubMed |
description | The nucleolus, whose primary function is ribosome biogenesis, plays an essential role in p53 activation. Ribosome biogenesis is inhibited in response to cellular stress and several nucleolar proteins translocate from the nucleolus to the nucleoplasm, where they activate p53. In this study, we analysed precisely how impaired ribosome biogenesis regulates the activation of p53 by depleting nucleolar factors involved in rRNA transcription or rRNA processing. Nucleolar RNA content decreased when rRNA transcription was inhibited. In parallel with the reduced levels of nucleolar RNA content, the nucleolar protein Myb-binding protein 1 A (MYBBP1A) translocated to the nucleoplasm and increased p53 acetylation. The acetylated p53 enhanced p21 and BAX expression and induced apoptosis. In contrast, when rRNA processing was inhibited, MYBBP1A remained in the nucleolus and nonacetylated p53 accumulated, causing cell cycle arrest at the G1 phase by inducing p21 but not BAX. We propose that the nucleolus functions as a stress sensor to modulate p53 protein levels and its acetylation status, determining cell fate between cell cycle arrest and apoptosis by regulating MYBBP1A translocation. |
format | Online Article Text |
id | pubmed-4456663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44566632015-06-12 Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A Kumazawa, Takuya Nishimura, Kazuho Katagiri, Naohiro Hashimoto, Sayaka Hayashi, Yuki Kimura, Keiji Sci Rep Article The nucleolus, whose primary function is ribosome biogenesis, plays an essential role in p53 activation. Ribosome biogenesis is inhibited in response to cellular stress and several nucleolar proteins translocate from the nucleolus to the nucleoplasm, where they activate p53. In this study, we analysed precisely how impaired ribosome biogenesis regulates the activation of p53 by depleting nucleolar factors involved in rRNA transcription or rRNA processing. Nucleolar RNA content decreased when rRNA transcription was inhibited. In parallel with the reduced levels of nucleolar RNA content, the nucleolar protein Myb-binding protein 1 A (MYBBP1A) translocated to the nucleoplasm and increased p53 acetylation. The acetylated p53 enhanced p21 and BAX expression and induced apoptosis. In contrast, when rRNA processing was inhibited, MYBBP1A remained in the nucleolus and nonacetylated p53 accumulated, causing cell cycle arrest at the G1 phase by inducing p21 but not BAX. We propose that the nucleolus functions as a stress sensor to modulate p53 protein levels and its acetylation status, determining cell fate between cell cycle arrest and apoptosis by regulating MYBBP1A translocation. Nature Publishing Group 2015-06-05 /pmc/articles/PMC4456663/ /pubmed/26044764 http://dx.doi.org/10.1038/srep10854 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Kumazawa, Takuya Nishimura, Kazuho Katagiri, Naohiro Hashimoto, Sayaka Hayashi, Yuki Kimura, Keiji Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A |
title | Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A |
title_full | Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A |
title_fullStr | Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A |
title_full_unstemmed | Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A |
title_short | Gradual reduction in rRNA transcription triggers p53 acetylation and apoptosis via MYBBP1A |
title_sort | gradual reduction in rrna transcription triggers p53 acetylation and apoptosis via mybbp1a |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456663/ https://www.ncbi.nlm.nih.gov/pubmed/26044764 http://dx.doi.org/10.1038/srep10854 |
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