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The nucleolus directly regulates p53 export and degradation
The correlation between stress-induced nucleolar disruption and abrogation of p53 degradation is evident after a wide variety of cellular stresses. This link may be caused by steps in p53 regulation occurring in nucleoli, as suggested by some biochemical evidence. Alternatively, nucleolar disruption...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171122/ https://www.ncbi.nlm.nih.gov/pubmed/21893597 http://dx.doi.org/10.1083/jcb.201105143 |
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author | Boyd, Mark T. Vlatković, Nikolina Rubbi, Carlos P. |
author_facet | Boyd, Mark T. Vlatković, Nikolina Rubbi, Carlos P. |
author_sort | Boyd, Mark T. |
collection | PubMed |
description | The correlation between stress-induced nucleolar disruption and abrogation of p53 degradation is evident after a wide variety of cellular stresses. This link may be caused by steps in p53 regulation occurring in nucleoli, as suggested by some biochemical evidence. Alternatively, nucleolar disruption also causes redistribution of nucleolar proteins, potentially altering their interactions with p53 and/or MDM2. This raises the fundamental question of whether the nucleolus controls p53 directly, i.e., as a site where p53 regulatory processes occur, or indirectly, i.e., by determining the cellular localization of p53/MDM2-interacting factors. In this work, transport experiments based on heterokaryons, photobleaching, and micronucleation demonstrate that p53 regulatory events are directly regulated by nucleoli and are dependent on intact nucleolar structure and function. Subcellular fractionation and nucleolar isolation revealed a distribution of ubiquitylated p53 that supports these findings. In addition, our results indicate that p53 is exported by two pathways: one stress sensitive and one stress insensitive, the latter being regulated by activities present in the nucleolus. |
format | Online Article Text |
id | pubmed-3171122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31711222012-03-05 The nucleolus directly regulates p53 export and degradation Boyd, Mark T. Vlatković, Nikolina Rubbi, Carlos P. J Cell Biol Research Articles The correlation between stress-induced nucleolar disruption and abrogation of p53 degradation is evident after a wide variety of cellular stresses. This link may be caused by steps in p53 regulation occurring in nucleoli, as suggested by some biochemical evidence. Alternatively, nucleolar disruption also causes redistribution of nucleolar proteins, potentially altering their interactions with p53 and/or MDM2. This raises the fundamental question of whether the nucleolus controls p53 directly, i.e., as a site where p53 regulatory processes occur, or indirectly, i.e., by determining the cellular localization of p53/MDM2-interacting factors. In this work, transport experiments based on heterokaryons, photobleaching, and micronucleation demonstrate that p53 regulatory events are directly regulated by nucleoli and are dependent on intact nucleolar structure and function. Subcellular fractionation and nucleolar isolation revealed a distribution of ubiquitylated p53 that supports these findings. In addition, our results indicate that p53 is exported by two pathways: one stress sensitive and one stress insensitive, the latter being regulated by activities present in the nucleolus. The Rockefeller University Press 2011-09-05 /pmc/articles/PMC3171122/ /pubmed/21893597 http://dx.doi.org/10.1083/jcb.201105143 Text en © 2011 Boyd et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Boyd, Mark T. Vlatković, Nikolina Rubbi, Carlos P. The nucleolus directly regulates p53 export and degradation |
title | The nucleolus directly regulates p53 export and degradation |
title_full | The nucleolus directly regulates p53 export and degradation |
title_fullStr | The nucleolus directly regulates p53 export and degradation |
title_full_unstemmed | The nucleolus directly regulates p53 export and degradation |
title_short | The nucleolus directly regulates p53 export and degradation |
title_sort | nucleolus directly regulates p53 export and degradation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171122/ https://www.ncbi.nlm.nih.gov/pubmed/21893597 http://dx.doi.org/10.1083/jcb.201105143 |
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