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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...

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Detalles Bibliográficos
Autores principales: Boyd, Mark T., Vlatković, Nikolina, Rubbi, Carlos P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
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.
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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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