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Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins
Nucleophosmin (NPM1) is a multifunctional protein that controls cell growth and genome stability via a mechanism that involves nucleolar–cytoplasmic shuttling. It is clear that NPM1 also contributes to the DNA damage response, yet its exact function is poorly understood. We recently linked NPM1 expr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019495/ https://www.ncbi.nlm.nih.gov/pubmed/24648491 http://dx.doi.org/10.1091/mbc.E13-12-0717 |
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author | Poletto, Mattia Lirussi, Lisa Wilson, David M. Tell, Gianluca |
author_facet | Poletto, Mattia Lirussi, Lisa Wilson, David M. Tell, Gianluca |
author_sort | Poletto, Mattia |
collection | PubMed |
description | Nucleophosmin (NPM1) is a multifunctional protein that controls cell growth and genome stability via a mechanism that involves nucleolar–cytoplasmic shuttling. It is clear that NPM1 also contributes to the DNA damage response, yet its exact function is poorly understood. We recently linked NPM1 expression to the functional activation of the major abasic endonuclease in mammalian base excision repair (BER), apurinic/apyrimidinic endonuclease 1 (APE1). Here we unveil a novel role for NPM1 as a modulator of the whole BER pathway by 1) controlling BER protein levels, 2) regulating total BER capacity, and 3) modulating the nucleolar localization of several BER enzymes. We find that cell treatment with the genotoxin cisplatin leads to concurrent relocalization of NPM1 and BER components from nucleoli to the nucleoplasm, and cellular experiments targeting APE1 suggest a role for the redistribution of nucleolar BER factors in determining cisplatin toxicity. Finally, based on the use of APE1 as a representative protein of the BER pathway, our data suggest a function for BER proteins in the regulation of ribogenesis. |
format | Online Article Text |
id | pubmed-4019495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-40194952014-07-30 Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins Poletto, Mattia Lirussi, Lisa Wilson, David M. Tell, Gianluca Mol Biol Cell Articles Nucleophosmin (NPM1) is a multifunctional protein that controls cell growth and genome stability via a mechanism that involves nucleolar–cytoplasmic shuttling. It is clear that NPM1 also contributes to the DNA damage response, yet its exact function is poorly understood. We recently linked NPM1 expression to the functional activation of the major abasic endonuclease in mammalian base excision repair (BER), apurinic/apyrimidinic endonuclease 1 (APE1). Here we unveil a novel role for NPM1 as a modulator of the whole BER pathway by 1) controlling BER protein levels, 2) regulating total BER capacity, and 3) modulating the nucleolar localization of several BER enzymes. We find that cell treatment with the genotoxin cisplatin leads to concurrent relocalization of NPM1 and BER components from nucleoli to the nucleoplasm, and cellular experiments targeting APE1 suggest a role for the redistribution of nucleolar BER factors in determining cisplatin toxicity. Finally, based on the use of APE1 as a representative protein of the BER pathway, our data suggest a function for BER proteins in the regulation of ribogenesis. The American Society for Cell Biology 2014-05-15 /pmc/articles/PMC4019495/ /pubmed/24648491 http://dx.doi.org/10.1091/mbc.E13-12-0717 Text en © 2014 Poletto et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Poletto, Mattia Lirussi, Lisa Wilson, David M. Tell, Gianluca Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins |
title | Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins |
title_full | Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins |
title_fullStr | Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins |
title_full_unstemmed | Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins |
title_short | Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins |
title_sort | nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019495/ https://www.ncbi.nlm.nih.gov/pubmed/24648491 http://dx.doi.org/10.1091/mbc.E13-12-0717 |
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