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p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen
The mechanisms by which TP53, the most frequently mutated gene in human cancer, suppresses tumorigenesis remain unclear. p53 modulates various cellular processes, such as apoptosis and proliferation, which has led to distinct cellular mechanisms being proposed for p53-mediated tumor suppression in d...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594498/ https://www.ncbi.nlm.nih.gov/pubmed/32886745 http://dx.doi.org/10.1083/jcb.201908212 |
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author | Valente, Liz J. Tarangelo, Amy Li, Albert Mao Naciri, Marwan Raj, Nitin Boutelle, Anthony M. Li, Yang Mello, Stephano Spano Bieging-Rolett, Kathryn DeBerardinis, Ralph J. Ye, Jiangbin Dixon, Scott J. Attardi, Laura D. |
author_facet | Valente, Liz J. Tarangelo, Amy Li, Albert Mao Naciri, Marwan Raj, Nitin Boutelle, Anthony M. Li, Yang Mello, Stephano Spano Bieging-Rolett, Kathryn DeBerardinis, Ralph J. Ye, Jiangbin Dixon, Scott J. Attardi, Laura D. |
author_sort | Valente, Liz J. |
collection | PubMed |
description | The mechanisms by which TP53, the most frequently mutated gene in human cancer, suppresses tumorigenesis remain unclear. p53 modulates various cellular processes, such as apoptosis and proliferation, which has led to distinct cellular mechanisms being proposed for p53-mediated tumor suppression in different contexts. Here, we asked whether during tumor suppression p53 might instead regulate a wide range of cellular processes. Analysis of mouse and human oncogene-expressing wild-type and p53-deficient cells in physiological oxygen conditions revealed that p53 loss concurrently impacts numerous distinct cellular processes, including apoptosis, genome stabilization, DNA repair, metabolism, migration, and invasion. Notably, some phenotypes were uncovered only in physiological oxygen. Transcriptomic analysis in this setting highlighted underappreciated functions modulated by p53, including actin dynamics. Collectively, these results suggest that p53 simultaneously governs diverse cellular processes during transformation suppression, an aspect of p53 function that would provide a clear rationale for its frequent inactivation in human cancer. |
format | Online Article Text |
id | pubmed-7594498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-75944982021-05-02 p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen Valente, Liz J. Tarangelo, Amy Li, Albert Mao Naciri, Marwan Raj, Nitin Boutelle, Anthony M. Li, Yang Mello, Stephano Spano Bieging-Rolett, Kathryn DeBerardinis, Ralph J. Ye, Jiangbin Dixon, Scott J. Attardi, Laura D. J Cell Biol Article The mechanisms by which TP53, the most frequently mutated gene in human cancer, suppresses tumorigenesis remain unclear. p53 modulates various cellular processes, such as apoptosis and proliferation, which has led to distinct cellular mechanisms being proposed for p53-mediated tumor suppression in different contexts. Here, we asked whether during tumor suppression p53 might instead regulate a wide range of cellular processes. Analysis of mouse and human oncogene-expressing wild-type and p53-deficient cells in physiological oxygen conditions revealed that p53 loss concurrently impacts numerous distinct cellular processes, including apoptosis, genome stabilization, DNA repair, metabolism, migration, and invasion. Notably, some phenotypes were uncovered only in physiological oxygen. Transcriptomic analysis in this setting highlighted underappreciated functions modulated by p53, including actin dynamics. Collectively, these results suggest that p53 simultaneously governs diverse cellular processes during transformation suppression, an aspect of p53 function that would provide a clear rationale for its frequent inactivation in human cancer. Rockefeller University Press 2020-09-04 /pmc/articles/PMC7594498/ /pubmed/32886745 http://dx.doi.org/10.1083/jcb.201908212 Text en © 2020 Valente et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Valente, Liz J. Tarangelo, Amy Li, Albert Mao Naciri, Marwan Raj, Nitin Boutelle, Anthony M. Li, Yang Mello, Stephano Spano Bieging-Rolett, Kathryn DeBerardinis, Ralph J. Ye, Jiangbin Dixon, Scott J. Attardi, Laura D. p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen |
title | p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen |
title_full | p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen |
title_fullStr | p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen |
title_full_unstemmed | p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen |
title_short | p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen |
title_sort | p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594498/ https://www.ncbi.nlm.nih.gov/pubmed/32886745 http://dx.doi.org/10.1083/jcb.201908212 |
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