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Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells
BACKGROUND: Tpr is a large coiled-coil protein located in the nuclear basket of the nuclear pore complex for which many different functions were proposed from yeast to human. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that depletion of Tpr by RNA interference triggers G0–G1 arrest and ultimately i...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139644/ https://www.ncbi.nlm.nih.gov/pubmed/21811608 http://dx.doi.org/10.1371/journal.pone.0022423 |
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author | David-Watine, Brigitte |
author_facet | David-Watine, Brigitte |
author_sort | David-Watine, Brigitte |
collection | PubMed |
description | BACKGROUND: Tpr is a large coiled-coil protein located in the nuclear basket of the nuclear pore complex for which many different functions were proposed from yeast to human. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that depletion of Tpr by RNA interference triggers G0–G1 arrest and ultimately induces a senescent-like phenotype dependent on the presence of p53. We also found that Tpr depletion impairs the NES [nuclear export sequence]-dependent nuclear export of proteins and causes partial co-depletion of Nup153. In addition Tpr depletion impacts on level and function of the SUMO-protease SENP2 thus affecting SUMOylation regulation at the nuclear pore and overall SUMOylation in the cell. CONCLUSIONS: Our data for the first time provide evidence that a nuclear pore component plays a role in controlling cellular senescence. Our findings also point to new roles for Tpr in the regulation of SUMO-1 conjugation at the nuclear pore and directly confirm Tpr involvement in the nuclear export of NES-proteins. |
format | Online Article Text |
id | pubmed-3139644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31396442011-08-02 Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells David-Watine, Brigitte PLoS One Research Article BACKGROUND: Tpr is a large coiled-coil protein located in the nuclear basket of the nuclear pore complex for which many different functions were proposed from yeast to human. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that depletion of Tpr by RNA interference triggers G0–G1 arrest and ultimately induces a senescent-like phenotype dependent on the presence of p53. We also found that Tpr depletion impairs the NES [nuclear export sequence]-dependent nuclear export of proteins and causes partial co-depletion of Nup153. In addition Tpr depletion impacts on level and function of the SUMO-protease SENP2 thus affecting SUMOylation regulation at the nuclear pore and overall SUMOylation in the cell. CONCLUSIONS: Our data for the first time provide evidence that a nuclear pore component plays a role in controlling cellular senescence. Our findings also point to new roles for Tpr in the regulation of SUMO-1 conjugation at the nuclear pore and directly confirm Tpr involvement in the nuclear export of NES-proteins. Public Library of Science 2011-07-19 /pmc/articles/PMC3139644/ /pubmed/21811608 http://dx.doi.org/10.1371/journal.pone.0022423 Text en Brigitte David-Watine. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article David-Watine, Brigitte Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells |
title | Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells |
title_full | Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells |
title_fullStr | Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells |
title_full_unstemmed | Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells |
title_short | Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells |
title_sort | silencing nuclear pore protein tpr elicits a senescent-like phenotype in cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139644/ https://www.ncbi.nlm.nih.gov/pubmed/21811608 http://dx.doi.org/10.1371/journal.pone.0022423 |
work_keys_str_mv | AT davidwatinebrigitte silencingnuclearporeproteintprelicitsasenescentlikephenotypeincancercells |