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Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair
Nucleophosmin (NPM) is an important phosphoprotein with pleiotropic functions in various cellular processes. Although phosphorylation has been postulated as an important functional determinant, possible regulatory roles of this modification on NPM are not fully characterized. Here, we find that NPM...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002393/ https://www.ncbi.nlm.nih.gov/pubmed/20962268 http://dx.doi.org/10.1091/mbc.E10-03-0239 |
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author | Lin, Chiao Yun Tan, Bertrand Chin-Ming Liu, Hsuan Shih, Chii-Jiun Chien, Kun-Yi Lin, Chih-Li Yung, Benjamin Yat-Ming |
author_facet | Lin, Chiao Yun Tan, Bertrand Chin-Ming Liu, Hsuan Shih, Chii-Jiun Chien, Kun-Yi Lin, Chih-Li Yung, Benjamin Yat-Ming |
author_sort | Lin, Chiao Yun |
collection | PubMed |
description | Nucleophosmin (NPM) is an important phosphoprotein with pleiotropic functions in various cellular processes. Although phosphorylation has been postulated as an important functional determinant, possible regulatory roles of this modification on NPM are not fully characterized. Here, we find that NPM is dephosphorylated on various threonine residues (Thr199 and Thr234/237) in response to UV-induced DNA damage. Further experiments indicate that the serine/threonine protein phosphatase PP1β is a physiological NPM phosphatase under both the genotoxic stress and growth conditions. As a consequence, NPM in its hypophosphorylated state facilitates DNA repair. Finally, our results suggest that one possible mechanism of this protective response lies in enhanced NPM-retinoblastoma tumor suppressor protein (pRB) interaction, leading to the relief of the repressive pRB–E2F1 circuitry and the consequent transcriptional activation of E2F1 and several downstream DNA repair genes. Thus, this study unveils a key phosphatase of NPM and highlights a novel mechanism by which the PP1β–NPM pathway contributes to cellular DNA damage response. |
format | Text |
id | pubmed-3002393 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30023932011-03-02 Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair Lin, Chiao Yun Tan, Bertrand Chin-Ming Liu, Hsuan Shih, Chii-Jiun Chien, Kun-Yi Lin, Chih-Li Yung, Benjamin Yat-Ming Mol Biol Cell Articles Nucleophosmin (NPM) is an important phosphoprotein with pleiotropic functions in various cellular processes. Although phosphorylation has been postulated as an important functional determinant, possible regulatory roles of this modification on NPM are not fully characterized. Here, we find that NPM is dephosphorylated on various threonine residues (Thr199 and Thr234/237) in response to UV-induced DNA damage. Further experiments indicate that the serine/threonine protein phosphatase PP1β is a physiological NPM phosphatase under both the genotoxic stress and growth conditions. As a consequence, NPM in its hypophosphorylated state facilitates DNA repair. Finally, our results suggest that one possible mechanism of this protective response lies in enhanced NPM-retinoblastoma tumor suppressor protein (pRB) interaction, leading to the relief of the repressive pRB–E2F1 circuitry and the consequent transcriptional activation of E2F1 and several downstream DNA repair genes. Thus, this study unveils a key phosphatase of NPM and highlights a novel mechanism by which the PP1β–NPM pathway contributes to cellular DNA damage response. The American Society for Cell Biology 2010-12-15 /pmc/articles/PMC3002393/ /pubmed/20962268 http://dx.doi.org/10.1091/mbc.E10-03-0239 Text en © 2010 by The American Society for Cell Biology 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). |
spellingShingle | Articles Lin, Chiao Yun Tan, Bertrand Chin-Ming Liu, Hsuan Shih, Chii-Jiun Chien, Kun-Yi Lin, Chih-Li Yung, Benjamin Yat-Ming Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair |
title | Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair |
title_full | Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair |
title_fullStr | Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair |
title_full_unstemmed | Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair |
title_short | Dephosphorylation of Nucleophosmin by PP1β Facilitates pRB Binding and Consequent E2F1-dependent DNA Repair |
title_sort | dephosphorylation of nucleophosmin by pp1β facilitates prb binding and consequent e2f1-dependent dna repair |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002393/ https://www.ncbi.nlm.nih.gov/pubmed/20962268 http://dx.doi.org/10.1091/mbc.E10-03-0239 |
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