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Pax8 has a critical role in epithelial cell survival and proliferation
The transcription factor Pax8, a member of the Paired-box gene family, is a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well characterized with respect to its role in regulating genes responsible for thyroid differentiation,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730432/ https://www.ncbi.nlm.nih.gov/pubmed/23868062 http://dx.doi.org/10.1038/cddis.2013.262 |
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author | Di Palma, T Filippone, M G Pierantoni, G M Fusco, A Soddu, S Zannini, M |
author_facet | Di Palma, T Filippone, M G Pierantoni, G M Fusco, A Soddu, S Zannini, M |
author_sort | Di Palma, T |
collection | PubMed |
description | The transcription factor Pax8, a member of the Paired-box gene family, is a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well characterized with respect to its role in regulating genes responsible for thyroid differentiation, its involvement in cell survival and proliferation has been hypothesized but remains unclear. Here, we show that Pax8 overexpression significantly increases proliferation and colony-forming efficiency of Fischer rat thyroid line 5 epithelial cells, although it is not sufficient to overcome their hormone dependence. More interestingly, we show that Pax8-specific silencing induces apoptosis through a p53-dependent pathway that involves caspase-3 activation and cleavage of poly(ADP)ribose polymerase. Our data indicate that tumor protein 53 induced nuclear protein 1 (tp53inp1), a positive regulator of p53-dependent cell cycle arrest and apoptosis, is a transcriptional target of Pax8 and is upregulated by Pax8 knockdown. Remarkably, tp53inp1 silencing significantly abolishes Pax8-induced apoptosis thus suggesting that tp53inp1 may be the mediator of the observed effects. In conclusion, our data highlight that Pax8 is required for the survival of differentiated epithelial cells and its expression levels are able to modulate the proliferation rate of such cells. |
format | Online Article Text |
id | pubmed-3730432 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-37304322013-08-01 Pax8 has a critical role in epithelial cell survival and proliferation Di Palma, T Filippone, M G Pierantoni, G M Fusco, A Soddu, S Zannini, M Cell Death Dis Original Article The transcription factor Pax8, a member of the Paired-box gene family, is a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well characterized with respect to its role in regulating genes responsible for thyroid differentiation, its involvement in cell survival and proliferation has been hypothesized but remains unclear. Here, we show that Pax8 overexpression significantly increases proliferation and colony-forming efficiency of Fischer rat thyroid line 5 epithelial cells, although it is not sufficient to overcome their hormone dependence. More interestingly, we show that Pax8-specific silencing induces apoptosis through a p53-dependent pathway that involves caspase-3 activation and cleavage of poly(ADP)ribose polymerase. Our data indicate that tumor protein 53 induced nuclear protein 1 (tp53inp1), a positive regulator of p53-dependent cell cycle arrest and apoptosis, is a transcriptional target of Pax8 and is upregulated by Pax8 knockdown. Remarkably, tp53inp1 silencing significantly abolishes Pax8-induced apoptosis thus suggesting that tp53inp1 may be the mediator of the observed effects. In conclusion, our data highlight that Pax8 is required for the survival of differentiated epithelial cells and its expression levels are able to modulate the proliferation rate of such cells. Nature Publishing Group 2013-07 2013-07-18 /pmc/articles/PMC3730432/ /pubmed/23868062 http://dx.doi.org/10.1038/cddis.2013.262 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Di Palma, T Filippone, M G Pierantoni, G M Fusco, A Soddu, S Zannini, M Pax8 has a critical role in epithelial cell survival and proliferation |
title | Pax8 has a critical role in epithelial cell survival and proliferation |
title_full | Pax8 has a critical role in epithelial cell survival and proliferation |
title_fullStr | Pax8 has a critical role in epithelial cell survival and proliferation |
title_full_unstemmed | Pax8 has a critical role in epithelial cell survival and proliferation |
title_short | Pax8 has a critical role in epithelial cell survival and proliferation |
title_sort | pax8 has a critical role in epithelial cell survival and proliferation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730432/ https://www.ncbi.nlm.nih.gov/pubmed/23868062 http://dx.doi.org/10.1038/cddis.2013.262 |
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