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The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death
The tumour suppressor p53 is an important mediator of cell cycle arrest and apoptosis in response to DNA damage, acting mainly by transcriptional regulation of specific target genes. The exact details how p53 modulates this decision on a molecular basis is still incompletely understood. One mechanis...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462756/ https://www.ncbi.nlm.nih.gov/pubmed/26062895 http://dx.doi.org/10.1038/srep11268 |
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author | Bock, Florian J. Tanzer, Maria C. Haschka, Manuel D. Krumschnabel, Gerhard Sohm, Bénédicte Goetsch, Katrin Kofler, Reinhard Villunger, Andreas |
author_facet | Bock, Florian J. Tanzer, Maria C. Haschka, Manuel D. Krumschnabel, Gerhard Sohm, Bénédicte Goetsch, Katrin Kofler, Reinhard Villunger, Andreas |
author_sort | Bock, Florian J. |
collection | PubMed |
description | The tumour suppressor p53 is an important mediator of cell cycle arrest and apoptosis in response to DNA damage, acting mainly by transcriptional regulation of specific target genes. The exact details how p53 modulates this decision on a molecular basis is still incompletely understood. One mechanism of regulation is acetylation of p53 on lysine K120 by the histone-acetyltransferase Tip60, resulting in preferential transcription of proapoptotic target genes. PDCD5, a protein with reported pro-apoptotic function, has recently been identified as regulator of Tip60-dependent p53-acetylation. In an effort to clarify the role of PDCD5 upon DNA damage, we generated cell lines in which PDCD5 expression was conditionally ablated by shRNAs and investigated their response to genotoxic stress. Surprisingly, we failed to note a rate-limiting role of PDCD5 in the DNA damage response. PDCD5 was dispensable for DNA damage induced apoptosis and cell cycle arrest and we observed no significant changes in p53 target gene transcription. While we were able to confirm interaction of PDCD5 with p53, we failed to do so for Tip60. Altogether, our results suggest a role of PDCD5 in the regulation of p53 function but unrelated to cell cycle arrest or apoptosis, at least in the cell types investigated. |
format | Online Article Text |
id | pubmed-4462756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44627562015-06-29 The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death Bock, Florian J. Tanzer, Maria C. Haschka, Manuel D. Krumschnabel, Gerhard Sohm, Bénédicte Goetsch, Katrin Kofler, Reinhard Villunger, Andreas Sci Rep Article The tumour suppressor p53 is an important mediator of cell cycle arrest and apoptosis in response to DNA damage, acting mainly by transcriptional regulation of specific target genes. The exact details how p53 modulates this decision on a molecular basis is still incompletely understood. One mechanism of regulation is acetylation of p53 on lysine K120 by the histone-acetyltransferase Tip60, resulting in preferential transcription of proapoptotic target genes. PDCD5, a protein with reported pro-apoptotic function, has recently been identified as regulator of Tip60-dependent p53-acetylation. In an effort to clarify the role of PDCD5 upon DNA damage, we generated cell lines in which PDCD5 expression was conditionally ablated by shRNAs and investigated their response to genotoxic stress. Surprisingly, we failed to note a rate-limiting role of PDCD5 in the DNA damage response. PDCD5 was dispensable for DNA damage induced apoptosis and cell cycle arrest and we observed no significant changes in p53 target gene transcription. While we were able to confirm interaction of PDCD5 with p53, we failed to do so for Tip60. Altogether, our results suggest a role of PDCD5 in the regulation of p53 function but unrelated to cell cycle arrest or apoptosis, at least in the cell types investigated. Nature Publishing Group 2015-06-11 /pmc/articles/PMC4462756/ /pubmed/26062895 http://dx.doi.org/10.1038/srep11268 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Bock, Florian J. Tanzer, Maria C. Haschka, Manuel D. Krumschnabel, Gerhard Sohm, Bénédicte Goetsch, Katrin Kofler, Reinhard Villunger, Andreas The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death |
title | The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death |
title_full | The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death |
title_fullStr | The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death |
title_full_unstemmed | The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death |
title_short | The p53 binding protein PDCD5 is not rate-limiting in DNA damage induced cell death |
title_sort | p53 binding protein pdcd5 is not rate-limiting in dna damage induced cell death |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462756/ https://www.ncbi.nlm.nih.gov/pubmed/26062895 http://dx.doi.org/10.1038/srep11268 |
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