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Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells
To fight resistances to radiotherapy, the understanding of escape mechanisms of tumor cells is crucial. The aim of this study was to identify phosphoproteins that are regulated upon irradiation. The comparative analysis of the phosphoproteome before and after irradiation brought nucleophosmin (NPM1)...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240713/ https://www.ncbi.nlm.nih.gov/pubmed/30453269 http://dx.doi.org/10.1016/j.tranon.2018.10.015 |
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author | Wiesmann, Nadine Gieringer, Rita Grus, Franz Brieger, Juergen |
author_facet | Wiesmann, Nadine Gieringer, Rita Grus, Franz Brieger, Juergen |
author_sort | Wiesmann, Nadine |
collection | PubMed |
description | To fight resistances to radiotherapy, the understanding of escape mechanisms of tumor cells is crucial. The aim of this study was to identify phosphoproteins that are regulated upon irradiation. The comparative analysis of the phosphoproteome before and after irradiation brought nucleophosmin (NPM1) into focus as a versatile phosphoprotein that has already been associated with tumorigenesis. We could show that knockdown of NPM1 significantly reduces tumor cell survival after irradiation. NPM1 is dephosphorylated stepwise within 1 hour after irradiation at two of its major phosphorylation sites: threonine-199 and threonine-234/237. This dephosphorylation is not the result of a fast cell cycle arrest, and we found a heterogenous intracellular distribution of NPM1 between the nucleoli, the nucleoplasm, and the cytoplasm after irradiation. We hypothesize that the dephosphorylation of NPM1 at threonine-199 and threonine-234/237 is part of the immediate response to irradiation and of importance for tumor cell survival. These findings could make NPM1 an attractive pharmaceutical target to radiosensitize tumor cells and improve the outcome of radiotherapy by inhibiting the pathways that help tumor cells to escape cell death after gamma irradiation. |
format | Online Article Text |
id | pubmed-6240713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62407132018-11-21 Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells Wiesmann, Nadine Gieringer, Rita Grus, Franz Brieger, Juergen Transl Oncol Original article To fight resistances to radiotherapy, the understanding of escape mechanisms of tumor cells is crucial. The aim of this study was to identify phosphoproteins that are regulated upon irradiation. The comparative analysis of the phosphoproteome before and after irradiation brought nucleophosmin (NPM1) into focus as a versatile phosphoprotein that has already been associated with tumorigenesis. We could show that knockdown of NPM1 significantly reduces tumor cell survival after irradiation. NPM1 is dephosphorylated stepwise within 1 hour after irradiation at two of its major phosphorylation sites: threonine-199 and threonine-234/237. This dephosphorylation is not the result of a fast cell cycle arrest, and we found a heterogenous intracellular distribution of NPM1 between the nucleoli, the nucleoplasm, and the cytoplasm after irradiation. We hypothesize that the dephosphorylation of NPM1 at threonine-199 and threonine-234/237 is part of the immediate response to irradiation and of importance for tumor cell survival. These findings could make NPM1 an attractive pharmaceutical target to radiosensitize tumor cells and improve the outcome of radiotherapy by inhibiting the pathways that help tumor cells to escape cell death after gamma irradiation. Neoplasia Press 2018-11-16 /pmc/articles/PMC6240713/ /pubmed/30453269 http://dx.doi.org/10.1016/j.tranon.2018.10.015 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Wiesmann, Nadine Gieringer, Rita Grus, Franz Brieger, Juergen Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells |
title | Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells |
title_full | Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells |
title_fullStr | Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells |
title_full_unstemmed | Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells |
title_short | Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells |
title_sort | phosphoproteome profiling reveals multifunctional protein npm1 as part of the irradiation response of tumor cells |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240713/ https://www.ncbi.nlm.nih.gov/pubmed/30453269 http://dx.doi.org/10.1016/j.tranon.2018.10.015 |
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